Novel small molecule inhibitors of tead transcription factors

ABSTRACT

The present disclosure compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the TEAD transcription factor, and are useful in the treatment of diseases related to the activity of TEAD transcription factor including, e.g., cancer and other diseases.

CLAIM OF PRIORITY

This application claims priority to U.S. Patent Application Ser. No.62/819,347, filed on Mar. 15, 2019, the entire contents of which arehereby incorporated by reference.

GOVERNMENT SUPPORT

This invention was made with government support under Grant Nos.1R01CA181537 and R01DK107651 awarded by the National Institutes ofHealth. The government has certain rights in the invention.

TECHNICAL FIELD

The present application is concerned with pharmaceutically usefulcompounds. The disclosure provides new compounds as well as theircompositions and methods of use. The compounds inhibit theautopalmitoylation of TEAD-transcription factors and are thereforeuseful in the treatment of diseases related to the activity ofTEAD-transcription factors including, e.g., cancers and other diseases.

BACKGROUND

Hippo signaling plays key roles in organ size control and tumorsuppression. The signal transduction involves a core kinase cascade,including MST1/2 and Lats1/2 kinases, leading to YAP/TAZphosphorylation, cytoplasmic retention and inhibition³. Physiological orpathological inactivation of these kinases leads to YAP/TAZdephosphorylation and nuclear accumulation. Subsequently, nuclearYAP/TAZ binds to the TEA domain transcription factors (TEAD1-4 inmammals, and Scalloped in Drosophila) to mediate the target genesexpression. The TEAD-YAP complex regulates normal development of skin,muscle, lung and liver, and are also oncogenic factor amplified in manyhuman cancers. TEADs can also bind to Vgll4, which has been implicatedas a tumor suppressor by competing with YAP/TAZ for TEADs binding.Therefore, TEADs are essential in regulating the transcriptional outputof Hippo pathway. Although targeting TEAD-YAP could be a promisingtherapeutic approach for diseases with deregulated Hippo pathway, itremains challenging to directly inhibit transcription factors with smallmolecules. Therefore, understanding the regulation of TEADs might revealnew therapeutic opportunities for drug discovery.

Post-translational S-palmitoylation attaches a 16-carbon palmitate tothe cysteine residue through a reversible thioester bond. A large numberof palmitoylated proteins have been identified through proteomicstudies. Dynamic S-palmitoylation plays critical roles regulating thetrafficking, membrane localization and functions of many proteins,including Src-family kinases, GTPases, and synaptic adhesion molecules.Asp-His-His-Cys (DHHC) family proteins are evolutionarily conservedprotein palmitoyl acyltransferases (PATs), mediating enzymaticS-palmitoylation. In addition, some proteins could bind topalmitoyl-Coenzyme A (CoA) directly, and undergo PAT-independentautopalmitoylation. However, autopalmitoylation is poorly characterized.Most of the reported examples of autopalmitoylation are observed undernon-physiological, high concentration of palmitoyl-CoA (>100 μM). Todate, only a few proteins, including yeast transporter protein Bet3, areautopalmitoylated under physiological concentrations of palmitoyl-CoA(1-10 μM). Therefore, it is important to reveal additionalautopalmitoylated proteins and to understand their regulations andfunctions.

SUMMARY

The present disclosure provides, inter alia, a compound of Formula (I):

or a pharmaceutically acceptable salt thereof; wherein the variables areas defined below.

The present disclosure also provides a composition comprising a compoundof Formula (I), or a pharmaceutically acceptable salt thereof, and atleast one pharmaceutically acceptable carrier.

The present disclosure also provides methods of treating cancer andother diseases comprising administering to a patient a therapeuticallyeffective amount of a compound of Formula (I), or a pharmaceuticallyacceptable salt thereof.

The details of one or more embodiments are set forth in the descriptionbelow. Other features, objects and advantages will be apparent from thedescription and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 scheme showing the structures of examples of compounds within thescope of the invention.

FIG. 2 is a scheme showing the structures of some reference compounds.

FIG. 3 is a picture showing the result of streptavidin and histidineblots showing the results of assays of the inhibition of TEAD2 in vitroautopalmitoylation by the compounds CP-1, flufenamic acid, CP-41, CP-42,CP-51, CP-52, CP-53, CP-54, CP-55, CP-56, CP-57, and CP-58.

FIG. 4 is a picture showing the result of streptavidin and histidineblots showing the results of assays of the inhibition of TEAD2 in vitroautopalmitoylation by the compound CP-55 at various concentrations.

FIG. 5 is a collection of plots showing inhibition of cell proliferationin the 92.1 uveal melanoma cell line, cellosaurus OCM1 cell line, humanhepatoma huh7 cell line, SNU398 human liver hepatocellular carcinomacell line, and the MDA-MB-453 human mammary gland metastatic carcinomacell line by the compound CP-55 at various concentrations.

FIG. 6 is collection of plots showing inhibition of gene expression forthe CYR61, CTGF and ANKRD1 genes in the huh7 human hepatoma cell line bythe compound CP-55 at various time points and concentrations.

FIG. 7 is a picture showing the result of streptavidin and histidineblots showing the results of assays of the inhibition of TEAD2 in vitroautopalmitoylation by the compound CP-58 at various concentrations.

FIG. 8 is a plot showing inhibition of cell proliferation in the 92.1uveal melanoma cell line by the compounds CP-1, CP-52, CP-55 and CP-58at various concentrations.

FIG. 9 is a plot showing inhibition of cell proliferation in the huh7human hepatoma cell line by the compound CP-57 at variousconcentrations.

FIG. 10 is a plot showing inhibition of cell proliferation in the huh7human hepatoma cell line by the compound CP-58 at variousconcentrations.

FIG. 11 is a pair of plots showing inhibition of gene expression for thegenes CYR61 and CTGF and ANKRD1 genes in the huh7 human hepatoma cellline by the compound CP-58 after 24 h compared to control.

FIG. 12 is a picture showing the result of streptavidin and histidineblots showing the results of assays of the inhibition of TEAD2 in vitroautopalmitoylation by the compounds CP-1, CP-55, CP-58, CP-59, CP-60,CP-61 and CP-62.

FIG. 13 is a plot inhibition of cell proliferation in the huh7 humanhepatoma cell line by the compounds CP-58, CP-59, CP-60, CP-61 and CP-62at various concentrations.

DETAILED DESCRIPTION

For the terms “e.g.” and “such as,” and grammatical equivalents thereof,the phrase “and without limitation” is understood to follow unlessexplicitly stated otherwise.

The singular forms “a,” “an,” and “the” include plural referents unlessthe context clearly dictates otherwise.

The term “about” means “approximately” (e.g., plus or minusapproximately 10% of the indicated value).

The expressions, “ambient temperature” and “room temperature”(abbreviated “r.t.”) refer generally to a temperature, e.g., a reactiontemperature, that is about the temperature of the room in which thereaction is carried out, e.g., a temperature from about 20° C. to about30° C., typically about 25° C.

Through proteomic and biochemical studies, it has been identified thatthe TEAD transcription factors are palmitoylated at evolutionarilyconserved cysteine residues. It has been found that TEADs undergoPAT-independent autopalmitoylation, under physiological concentrationsof palmitoyl-CoA. The crystal structures of the lipid-bound TEADs, andrevealed a new ligand-binding site in TEADs. Furthermore,autopalmitoylation plays critical roles in regulating TEAD-YAPassociation and their physiological functions in vitro and in vivo.Therefore, palmitoylation of TEADs plays important roles in regulatingHippo pathway transcriptional complexes.

The discovery of a new ligand-binding site in TEADs has allowed thediscovery of small molecule inhibitors of TEAD autopalmitoylation. Whilenot being bound by any theory, it is understood that the ligands bind tothe palmitate-binding pocket, and inhibit TEAD-YAP interaction, cancercell proliferation and migration. Therefore, direct inhibition of TEADautopalmitoylation activities is useful to inhibit these oncogenictranscription factors.

I. Compounds

The present disclosure provides, inter alia, a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

-   -   L¹ is absent, or a group of formula N(R^(N)) or C(O);    -   D is a group of formula (D1), (D2), (D3), (D4), (D5), (D6) or        (D7):

-   -   m is 1, 2 or 3;    -   A¹ is C(O)R¹, S(O)₂R¹, NHC(O)R¹, (C₁₋₃ alkylene)-C(O)R¹, NH(C₁₋₃        alkylene)-C(O)R¹, CN, NO₂, 5-10 membered heteroaryl, 4-10        membered heterocycloalkyl, (C₁₋₃ alkylene)-5-10 membered        heteroaryl, or (C₁₋₃ alkylene)-4-10 membered heterocycloalkyl,        wherein the (C₁₋₃ alkylene) group of the (C₁₋₃ alkylene)-C(O)R¹        group forming A¹ is unsubstituted or substituted by 1, 2, 3, 4        or 5 substituents each independently selected from halogen,        OR^(a1), NR^(c1)R^(d1), NR^(a1)(CO)(C₁₋₆ alkyl), and        NR^(a1)(CO)O(C₁₋₆ alkyl); and wherein the 5-10 membered        heteroaryl, 4-10 membered heterocycloalkyl, (C₁₋₃ alkylene)-5-10        membered heteroaryl, or (C₁₋₃ alkylene)-4-10 membered        heterocycloalkyl forming A¹ is unsubstituted or substituted by        1, 2, 3, 4 or 5 substituents each independently selected from        halogen, OR^(a1), SR^(a1), C(O)OR^(a1), NR^(c1)R^(d1), and        C(O)NR^(c1)R^(d1);    -   L² is absent, or a group of formula N(R^(N)), O, or C(O);    -   L³ is absent or a group of formula CH₂, C≡C, N(R^(N)) or C(O);    -   each R^(N) is independently H, C₁₋₆ alkyl, C(O)C₁₋₆ alkyl, or        C(O)OC₁₋₆ alkyl;    -   R¹ is H, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, Cy^(1A), OH,        OC₁₋₆ alkyl, OCy^(1A)O(C₁₋₃ alkylenyl)Cy^(1A), NH₂, NHC₁₋₆        alkyl, N(C₁₋₆ alkyl)₂, NHCy^(1A), NH(C₁₋₃ alkylenyl)Cy^(1A),        N(C₁₋₆ alkyl)Cy^(1A), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(1A),        wherein each of the C₁₋₆ alkyl forming R¹ is unsubstituted or        substituted by 1, 2, 3, 4 or 5 substituents each independently        selected from halogen, OR^(a1), SR^(a1), and NR^(c1)R^(d1);    -   Cy^(1A) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered        heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of        the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or        4-10 membered heterocycloalkyl forming Cy^(1A) is unsubstituted        or substituted by 0, 1 or 2 Cy^(1B) and 0, 1, 2, 3, 4 or 5        substituents each independently selected from unsubstituted C₁₋₆        alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), NR^(c1)R^(d1), and C₁₋₆ alkyl that is        substituted by 1, 2, or 3 substituents each independently        selected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), and        NR^(c1)R^(d1);    -   each Cy^(1B) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered        heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of        the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or        4-10 membered heterocycloalkyl forming Cy^(1B) is unsubstituted        or substituted by 1, 2, 3, 4 or 5 substituents each        independently selected from unsubstituted C₁₋₆ alkyl, C₂₋₆        alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1)        SR^(a1), and NR^(c1)R^(d1); and C₁₋₆ alkyl that is substituted        by 1, 2, or 3 substituents each independently selected from        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), and        NR^(c1)R^(d1);    -   A² is CR² or N;    -   A³ is CR³ or N;    -   A⁴ is CR⁴ or N;    -   A⁵ is CR⁵ or N;    -   A⁶ is CR⁶ or N;    -   A⁷ is CR⁷ or N;    -   A⁸ is CR⁸ or N;    -   A⁹ is CR⁹ or N;    -   A¹⁰ is CR¹⁰ or N;    -   A^(D41) is CH, C(C₁₋₆ alkyl) or N;    -   A^(D42) is CH₂, NH or NC₁₋₆ alkyl;    -   R² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),        C(O)OR^(a1), C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted        by 1, 2, or 3 substituents each independently selected from        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), and        NR^(c1)R^(d1);    -   R³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),        C(O)OR^(a1), C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted        by 1, 2, or 3 substituents each independently selected from        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), and        NR^(c1)R^(d1);    -   R⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),        C(O)OR^(a1), C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted        by 1, 2, or 3 substituents each independently selected from        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), and        NR^(c1)R^(d1);    -   R⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),        C(O)OR^(a1), C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted        by 1, 2, or 3 substituents each independently selected from        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), and        NR^(c1)R^(d1);    -   R⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), S(O)₂R^(b1),        S(O)₂NR^(c1)R^(d1), NR^(c1)R^(d1), C(O)OR^(a1),        C(O)NR^(c1)R^(d1), Cy^(7A), OCy^(7A), O(C₁₋₃ alkylenyl)Cy^(7A),        C(O)OCy^(7A), C(O)O(C₁₋₃ alkylenyl)Cy^(7A), NHCy^(7A)NH(C₁₋₃        alkylenyl)Cy^(7A), N(C₁₋₆ alkyl)Cy^(7A), N(C(O)C₁₋₆        alkyl)Cy^(7A), N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7A),        C(O)NHCy^(7A), C(O)NH(C₁₋₃ alkylenyl)Cy^(7A), C(O)N(C₁₋₆        alkyl)Cy^(7A), C(O)N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7A), or C₁₋₆        alkyl that is substituted by 1, 2, or 3 substituents each        independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), and NR^(c1)R^(d1);    -   R⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),        C(O)OR^(a1), S(O)₂NR^(c1)R^(d1), C(O)NR^(c1)R^(d1), Cy^(7A),        OCy^(7A), O(C₁₋₃ alkylenyl)Cy^(7A), C(O)OCy^(7A), C(O)O(C₁₋₃        alkylenyl)Cy^(7A), NHCy^(7A), NH(C₁₋₃ alkylenyl)Cy^(7A), N(C₁₋₆        alkyl)Cy^(7A), N(C(O)C₁₋₆ alkyl)Cy^(7A), N(C₁₋₆ alkyl)(C₁₋₃        alkylenyl)Cy^(7A), C(O)NHCy^(7A), C(O)NH(C₁₋₃ alkylenyl)Cy^(7A),        C(O)N(C₁₋₆ alkyl)Cy^(7A), C(O)N(C₁₋₆ alkyl)(C₁₋₃        alkylenyl)Cy^(7A) or C₁₋₆ alkyl that is substituted by 1, 2, or        3 substituents each independently selected from halogen, C₁₋₆        haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);    -   Cy^(7A) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered        heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of        the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or        4-10 membered heterocycloalkyl forming Cy^(7A) is unsubstituted        or substituted by 0, 1 or 2 substituents selected from Cy^(7B),        OCy^(7B), NHCy^(7B), and C(O)NHCy^(7B), and 0, 1, 2, 3, 4 or 5        substituents each independently selected from unsubstituted C₁₋₆        alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1),        and C₁₋₆ alkyl that is substituted by 1, 2, or 3 substituents        each independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), and NR^(c1)R^(d1);    -   each Cy^(7B) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered        heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of        the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or        4-10 membered heterocycloalkyl forming Cy^(7B) is unsubstituted        or substituted by 1, 2, 3, 4 or 5 substituents each        independently selected from unsubstituted C₁₋₆ alkyl, C₂₋₆        alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),        SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆        alkyl that is substituted by 1, 2, or 3 substituents each        independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), NR^(c1)R^(d1);    -   R⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), S(O)₂NR^(c1)R^(d1),        SR^(a1), NR^(c1)R^(d1), NR^(c1)S(O)₂R^(b1), C(O)OR^(a1),        C(O)NR^(c1)R^(d1), Cy^(8A), OH, OCy^(8A), O(C₁₋₃        alkylenyl)Cy^(8A), C(O)OCy^(8A), C(O)O(C₁₋₃ alkylenyl)Cy^(8A),        NHCy^(8A), N(Cy^(8A))₂, NH(C₁₋₃ alkylenyl)Cy^(8A), N(C₁₋₆        alkyl)Cy^(8A), N(C(O)C₁₋₆ alkyl)Cy^(8A), SO₂NHCy^(8A), N(C₁₋₆        alkyl)(C₁₋₃ alkylenyl)Cy^(8A), C(O)NHCy^(8A), C₁₋₃        alkylene-C(O)NHCy^(8A), C(O)NH(C₁₋₃ alkylenyl)Cy^(8A),        C(O)N(C₁₋₆ alkyl)Cy^(8A), C(O)N(C₁₋₆ alkyl)(C₁₋₃        alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or        3 substituents each independently selected from halogen, C₁₋₆        haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);    -   Cy^(8A) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered        heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of        the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or        4-10 membered heterocycloalkyl forming Cy^(8A) is unsubstituted        or substituted by 0, 1 or 2 substituents selected from Cy^(8B),        OCy^(8B), NHCy^(8B), and C(O)NHCy^(8B), and 0, 1, 2, 3, 4 or 5        substituents each independently selected from unsubstituted C₁₋₆        alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1),        and C₁₋₆ alkyl that is substituted by 1, 2, or 3 substituents        each independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), and NR^(c1)R^(d1);    -   each Cy^(8B) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered        heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of        the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or        4-10 membered heterocycloalkyl forming Cy^(8B) is unsubstituted        or substituted by 1, 2, 3, 4 or 5 substituents each        independently selected from unsubstituted C₁₋₆ alkyl, C₂₋₆        alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1)        SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆        alkyl that is substituted by 1, 2, or 3 substituents each        independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), and NR^(c1)R^(d1);    -   R⁹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),        NR^(c1)C(O)R^(b1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), or C₁₋₆ alkyl        that is substituted by 1, 2, or 3 substituents each        independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), and NR^(c1)R^(d1);    -   R¹⁰ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),        C(O)OR^(a1), C(O)NR^(c1)R^(d1), or C₁₋₆ alkyl that is        substituted by 1, 2, or 3 substituents each independently        selected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), and        NR^(c1)R^(d1);    -   Cy^(D71) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-14 membered        heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of        the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or        4-10 membered heterocycloalkyl forming Cy^(D71) is unsubstituted        or substituted by 0, 1 or 2 substituents selected from Cy^(D72),        CH₂Cy^(D72), OCy^(D72), NHCy^(D72), O—C₁₋₆ alkylene-Cy^(D72),        N(C₁₋₆ alkyl)Cy^(D72), N(C(O)C₁₋₆ alkyl)Cy^(D72), and        C(O)NHCy^(D72), and 0, 1, 2, 3, 4 or 5 substituents each        independently selected from unsubstituted C₁₋₆ alkyl, C₂₋₆        alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),        S(hal)₅, SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1),        and C₁₋₆ alkyl or C₂₋₆ alkenyl that is substituted by 1, 2, or 3        substituents each independently selected from halogen, C₁₋₆        haloalkyl, CN, OR^(a1), SR^(a1), C(O)OR^(a1), and NR^(c1)R^(d1);    -   each Cy^(D72) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered        heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of        the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or        4-10 membered heterocycloalkyl forming Cy^(D72) is unsubstituted        or substituted by 1, 2, 3, 4 or 5 substituents each        independently selected from unsubstituted C₁₋₆ alkyl, C₂₋₆        alkenyl, C₂₋₆ alkynyl, C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 4-10        membered heterocycloalkyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),        SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆        alkyl that is substituted by 1, 2, or 3 substituents each        independently selected from C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 4-10        membered heterocycloalkyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),        SR^(a1), C(O)OR^(a1), and NR^(c1)R^(d1), wherein said C₆₋₁₀        aryl, C₃₋₁₅ cycloalkyl, and 4-10 membered heterocycloalkyl are        each optionally substituted with 1, 2, or 3 substituents        independently selected from C₁₋₆ alkyl, halogen, C₁₋₆ haloalkyl,        CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), and        C(O)NR^(c1)R^(d1); and    -   R^(a1), R^(b1), R^(c1) and R^(d1) are each independently        selected from H, C₁₋₆ alkyl, C₁₋₆ haloalkyl, HO—C₁₋₆ alkylene,        amino-C₁₋₆ alkylene, C₁₋₆ alkylamino-C₁₋₆ alkylene, di(C₁₋₆        alkyl)amino-C₁₋₆ alkylene, C₁₋₆ alkoxy-C₁₋₆ alkylene, C₆₋₁₀        aryl, C₂₋₆ alkenyl and C₂₋₆ alkynyl; or    -   R^(c1) and R^(d1) together with the nitrogen atom to which they        are both attached together form a 4-10 membered unsubstituted        heterocycloalkyl ring or a heterocyclic ring that is substituted        with 1, 2, or 3 substituents independently selected from C₁₋₆        alkyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1),        NR^(c1)R^(d1), C(O)OR^(a1), and C(O)NR^(c1)R^(d1);    -   provided:    -   L¹ is a group of formula N(R^(N)) when L² is C(O);    -   L¹ is a group of formula C(O) when L² is N(R^(N));    -   L² is absent, or a group of formula N(R^(N)) when L¹ is C(O);    -   L² is absent, or a group of formula C(O) when L¹ is N(R^(N));    -   A^(D41) is CH, C(C₁₋₆ alkyl) when A^(D42) is NH or NC₁₋₆ alkyl;    -   A^(D42) is CH₂ when A^(D41) is NH or NC₁₋₆ alkyl;    -   no more than two of A², A³, A⁴ and A⁵ is N;    -   no more than two of A⁶, A⁷, A⁸, A⁹ and A¹⁰ is N; and    -   either R¹ is present and is Cy^(1A), OCy^(1A), O(C₁₋₃        alkylenyl)Cy^(1A), NHCy^(1A) NH(C₁₋₃ alkylenyl)Cy^(1A), N(C₁₋₆        alkyl)Cy^(1A), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(1A); or    -   R⁷ is Cy^(7A), OCy^(7A), O(C₁₋₃ alkylenyl)Cy^(7A), C(O)OCy^(7A),        C(O)O(C₁₋₃ alkylenyl)Cy^(7A), NHCy^(7A), NH(C₁₋₃        alkylenyl)Cy^(7A), N(C₁₋₆ alkyl)Cy^(7A), N(C₁₋₆ alkyl)(C₁₋₃        alkylenyl)Cy^(7A); C(O)NHCy^(7A), C(O)NH(C₁₋₃ alkylenyl)Cy^(7A),        C(O)N(C₁₋₆ alkyl)Cy^(7A), or C(O)N(C₁₋₆ alkyl)(C₁₋₃        alkylenyl)Cy^(7A), or    -   R⁸ is Cy^(8A), OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), C(O)OCy^(8A),        C(O)O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃        alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), N(C₁₋₆ alkyl)(C₁₋₃        alkylenyl)Cy^(8A), C(O)NHCy^(8A), C(O)NH(C₁₋₃ alkylenyl)Cy^(8A),        C(O)N(C₁₋₆ alkyl)Cy^(8A), or C(O)N(C₁₋₆ alkyl)(C₁₋₃        alkylenyl)Cy^(8A).

The present disclosure provides, inter alia, a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

L¹ is absent, or a group of formula N(R^(N)) or C(O);

D is a group of formula (D1), (D2), (D3), (D4), (D5), (D6), or (D7):

m is 1, 2 or 3;

A¹ is C(O)R¹, S(O)₂R¹, NHC(O)R¹, (C₁₋₃ alkylene)-C(O)R¹, NH(C₁₋₃alkylene)-C(O)R¹, CN, NO₂, 5-10 membered heteroaryl, 4-10 memberedheterocycloalkyl, (C₁₋₃ alkylene)-5-10 membered heteroaryl, or (C₁₋₃alkylene)-4-10 membered heterocycloalkyl, wherein the (C₁₋₃ alkylene)group of the (C₁₋₃ alkylene)-C(O)R¹ group forming A¹ is unsubstituted orsubstituted by 1, 2, 3, 4 or 5 substituents each independently selectedfrom halogen, OR^(a1), NR^(c1)R^(d1), NR^(a1)(CO)(C₁₋₆ alkyl), andNR^(a1)(CO)O(C₁₋₆ alkyl); and wherein the 5-10 membered heteroaryl, 4-10membered heterocycloalkyl, (C₁₋₃ alkylene)-5-10 membered heteroaryl, or(C₁₋₃ alkylene)-4-10 membered heterocycloalkyl forming A¹ isunsubstituted or substituted by 1, 2, 3, 4 or 5 substituents eachindependently selected from halogen, OR^(a1), SR^(a1), C(O)OR^(a1),NR^(c1)R^(d1) and C(O)NR^(c1)R^(d1);

L² is absent, or a group of formula N(R^(N)), O, or C(O);

L³ is absent or a group of formula CH₂, C≡C, N(R^(N)) or C(O);

each R^(N) is independently H, C₁₋₆ alkyl, C(O)C₁₋₆ alkyl, or C(O)OC₁₋₆alkyl;

R¹ is H, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, Cy^(1A), OH, OC₁₋₆alkyl, OCy^(1A), O(C₁₋₃ alkylenyl)Cy^(1A), NH₂, NHC₁₋₆ alkyl, N(C₁₋₆alkyl)₂, NHCy^(1A), NH(C₁₋₃ alkylenyl)Cy^(1A), N(C₁₋₆ alkyl)Cy^(1A), orN(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(1A), wherein each of the C₁₋₆ alkylforming R¹ is unsubstituted or substituted by 1, 2, 3, 4 or 5substituents each independently selected from halogen, OR^(a1), SR^(a1),and NR^(c1)R^(d1);

Cy^(1A) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or4-10 membered heterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkylforming Cy^(1A) is unsubstituted or substituted by 0, 1 or 2 Cy^(1B) and0, 1, 2, 3, 4 or 5 substituents each independently selected fromunsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1) and C₁₋₆ alkyl that issubstituted by 1, 2, or 3 substituents each independently selected fromhalogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

each Cy^(1B) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl,or 4-10 membered heterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkylforming Cy^(1B) is unsubstituted or substituted by 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), and NR^(c1)R^(d1); and C₁₋₆ alkyl that is substituted by 1, 2,or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

A² is CR² or N;

A³ is CR³ or N;

A⁴ is CR⁴ or N;

A⁵ is CR⁵ or N;

A⁶ is CR⁶ or N;

A⁷ is CR⁷ or N;

A⁸ is CR⁸ or N;

A⁹ is CR⁹ or N;

A¹⁰ is CR¹⁰ or N;

A^(D41) is CH, C(C₁₋₆ alkyl) or N;

A^(D42) is CH₂, NH or NC₁₋₆ alkyl;

R² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1), Cy^(7A), OCy^(7A), O(C₁₋₃ alkylenyl)Cy^(7A),C(O)OCy^(7A), C(O)O(C₁₋₃ alkylenyl)Cy^(7A), NHCy^(7A), NH(C₁₋₃alkylenyl)Cy^(7A), N(C₁₋₆ alkyl)Cy^(7A), N(C(O)C₁₋₆ alkyl)Cy^(7A),N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7A), C(O)NHCy^(7A), C(O)NH(C₁₋₃alkylenyl)Cy^(7A), C(O)N(C₁₋₆ alkyl)Cy^(7A), C(O)N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7A) or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

Cy^(7A) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or4-10 membered heterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkylforming Cy^(7A) is unsubstituted or substituted by 0, 1 or 2substituents selected from Cy^(7B), OCy^(7B), NHCy^(7B), andC(O)NHCy^(7B), and 0, 1, 2, 3, 4 or 5 substituents each independentlyselected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

each Cy^(7B) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl,or 4-10 membered heterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkylforming Cy^(7B) is unsubstituted or substituted by 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1),NR^(c1)R^(d1);

R⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1), Cy^(8A), OH, OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A),C(O)OCy^(8A), C(O)O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), N(Cy^(8A))₂,NH(C₁₋₃ alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), N(C(O)C₁₋₆alkyl)Cy^(8A), SO₂NHCy^(8A), N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(8A),C(O)NHCy^(8A), C₁₋₃ alkylene-C(O)NHCy^(8A), C(O)NH(C₁₋₃alkylenyl)Cy^(8A), C(O)N(C₁₋₆ alkyl)Cy^(8A), C(O)N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

Cy^(8A) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or4-10 membered heterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkylforming Cy^(8A) is unsubstituted or substituted by 0, 1 or 2substituents selected from Cy^(8B), OCy^(8B), NHCy^(8B), andC(O)NHCy^(8B), and 0, 1, 2, 3, 4 or 5 substituents each independentlyselected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

each Cy^(8B) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl,or 4-10 membered heterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkylforming Cy^(8B) is unsubstituted or substituted by 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1);

R⁹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁰ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

Cy^(D71) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-14 membered heteroaryl, or4-10 membered heterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkylforming Cy^(D71) is unsubstituted or substituted by 0, 1 or 2substituents selected from Cy^(D72), CH₂Cy^(D72), OCy^(D72), NHCy^(D72),O—C₁₋₆ alkylene-Cy^(D72), N(C₁₋₆ alkyl)Cy^(D72), N(C(O)C₁₋₆alkyl)Cy^(D72), and C(O)NHCy^(D72), and 0, 1, 2, 3, 4 or 5 substituentseach independently selected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1),NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆ alkyl or C₂₋₆alkenyl that is substituted by 1, 2, or 3 substituents eachindependently selected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), C(O)OR^(a1), and NR^(c1)R^(d1);

each Cy^(D72) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl,or 4-10 membered heterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkylforming Cy^(D72) is unsubstituted or substituted by 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₁₅ cycloalkyl, halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), andC₁₋₆ alkyl that is substituted by 1, 2, or 3 substituents eachindependently selected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), C(O)OR^(a1), and NR^(c1)R^(d1); and

R^(a1), R^(b1), R^(c1) and R^(d1) are each independently selected fromH, C₁₋₆ alkyl, HO—C₁₋₆ alkylene, C₁₋₆ alkoxy-C₁₋₆ alkylene, C₆₋₁₀ aryl,C₂₋₆ alkenyl and C₂₋₆ alkynyl; or

R^(c1) and R^(d1) together with the nitrogen atom to which they are bothattached together form a 4-10 membered unsubstituted heterocycloalkylring;

In some embodiments:

L¹ is a group of formula N(R^(N)) when L² is C(O);

L¹ is a group of formula C(O) when L² is N(R^(N));

L² is absent, or a group of formula N(R^(N)) when L¹ is C(O);

L² is absent, or a group of formula C(O) when L¹ is N(R^(N));

A^(D41) is CH, C(C₁₋₆ alkyl) when A^(D42) is NH or NC₁₋₆ alkyl;

A^(D42) is CH₂ when A^(D41) is NH or NC₁₋₆ alkyl;

no more than two of A², A³, A⁴ and A⁵ is N;

no more than two of A⁶, A⁷, A⁸, A⁹ and A¹⁰ is N; and

either R¹ is present and is Cy^(1A), OCy^(1A), O(C₁₋₃ alkylenyl)Cy^(1A),NHCy^(1A) NH(C₁₋₃ alkylenyl)Cy^(1A), N(C₁₋₆ alkyl)Cy^(1A), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(1A); or

R⁷ is Cy^(7A), OCy^(7A), O(C₁₋₃ alkylenyl)Cy^(7A) C(O)OCy^(7A),C(O)O(C₁₋₃ alkylenyl)Cy^(7A), NHCy^(7A), NH(C₁₋₃ alkylenyl)Cy^(7A),N(C₁₋₆ alkyl)Cy^(7A), N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7A);C(O)NHCy^(7A), C(O)NH(C₁₋₃ alkylenyl)Cy^(7A), C(O)N(C₁₋₆ alkyl)Cy^(7A),or C(O)N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7A), or

R⁸ is Cy^(8A), OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), C(O)OCy^(8A),C(O)O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃ alkylenyl)Cy^(8A),N(C₁₋₆ alkyl)Cy^(8A), N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(8A),C(O)NHCy^(8A), C(O)NH(C₁₋₃ alkylenyl)Cy^(8A), C(O)N(C₁₋₆ alkyl)Cy^(8A),or C(O)N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(8A).

In some embodiments, L¹ is absent.

In some embodiments, L¹ is N(R^(N)), e.g., NH or NMe.

In some embodiments, L¹ is C(O).

In some embodiments, D is a group of formula (D1).

In some embodiments, D is a group of formula (D2).

In some embodiments, D is a group of formula (D3).

In some embodiments, D is a group of formula (D4).

In some embodiments, D is a group of formula (D5).

In some embodiments, D is a group of formula (D6).

In some embodiments, D is a group of formula (D7).

In some embodiments, A¹ is C(O)R¹, e.g., C(O)OH.

In some embodiments, A¹ is S(O)₂R¹.

In some embodiments, A¹ is NHC(O)R¹.

In some embodiments, A¹ is NH(C₁₋₃ alkylene)-C(O)R¹.

In some embodiments, wherein A¹ is (C₁₋₃ alkylene)-C(O)R¹, wherein the(C₁₋₃ alkylene) group of the (C₁₋₃ alkylene)-C(O)R¹ group forming A¹ isunsubstituted or substituted by 0, 1, 2, 3, 4 or 5 substituents eachindependently selected from halogen, OR^(a1), NR^(c1)R^(d1),NR^(a1)(CO)(C₁₋₆ alkyl), and NR^(a1)(CO)O(C₁₋₆ alkyl).

In some embodiments, A¹ is (C₁₋₃ alkylene)-C(O)R¹, wherein the (C₁₋₃alkylene) group of the (C₁₋₃ alkylene)-C(O)R¹ group forming A¹ issubstituted by NR^(c1)R^(d1), NR^(a1)(CO)(C₁₋₆ alkyl), orNR^(a1)(CO)O(C₁₋₆ alkyl), e.g., CH₂CH(NH₂)C(O)OH.

In some embodiments, A¹ is CN.

In some embodiments, A¹ is NO₂.

In some embodiments, A¹ is 5-10 membered heteroaryl, 4-10 memberedheterocycloalkyl, (C₁₋₃ alkylene)-5-10 membered heteroaryl, or (C₁₋₃alkylene)-4-10 membered heterocycloalkyl that is unsubstituted orsubstituted by 0, 1, 2, 3, 4 or 5 substituents each independentlyselected from halogen, OR^(a1), SR^(a1), C(O)OR^(a1), NR^(c1)R^(d1) andC(O)NR^(c1)R^(d1).

In some embodiments, A¹ is 5-10 membered heteroaryl, 4-10 memberedheterocycloalkyl, CH₂(5-10 membered heteroaryl), or CH₂(4-10 memberedheterocycloalkyl) that is unsubstituted or substituted by 1, 2, 3, 4 or5 substituents each independently selected from halogen, OR^(a1),SR^(a1), C(O)OR^(a1), NR^(c1)R^(d1) and C(O)NR^(c1)R^(d1).

In some embodiments, A² is CR².

In some embodiments, R² is H.

In some embodiments, A² is N.

In some embodiments, A³ is CR³.

In some embodiments, R³ is H, C₁₋₆ alkyl or C₁₋₆ haloalkyl.

In some embodiments, R³ is H, methyl or trifluoroethyl.

In some embodiments, R³ is H.

In some embodiments, A³ is N.

In some embodiments, A⁴ is CR⁴.

In some embodiments, R⁴ is H.

In some embodiments, A⁴ is N.

In some embodiments, A⁵ is CR⁵.

In some embodiments, R⁵ is H.

In some embodiments, A⁵ is N.

In some embodiments, A² is CR², A³ is CR³, A⁴ is CR⁴, and A⁵ is CR⁵.

In some embodiments, A² is CR², A³ is CR³, A⁴ is CR⁴, and A⁵ is N.

In some embodiments, D is a group of formula (D4).

In some embodiments, A^(D41) is CH

In some embodiments, A^(D41) is C(C₁₋₆ alkyl).

In some embodiments, A^(D41) is N.

In some embodiments, A^(D42) is NH.

In some embodiments, A^(D42) is NC₁₋₆ alkyl, e.g., NMe.

In some embodiments, A^(D42) is CH₂.

In some embodiments, D is a group of formula (D4) and m is 1.

In some embodiments, D is a group of formula (D4) and m is 2.

In some embodiments, D is a group of formula (D4) and m is 3.

In some embodiments, D is a group of formula (D5).

In some embodiments, D is a group of formula (D5) and m is 1.

In some embodiments, D is a group of formula (D5) and m is 2.

In some embodiments, D is a group of formula (D5) and m is 3.

In some embodiments, D is a group of formula (D6).

In some embodiments, D is a group of formula (D6) and m is 1.

In some embodiments, D is a group of formula (D6) and m is 2.

In some embodiments, D is a group of formula (D6) and m is 3.

In some embodiments, D is a group of formula (D7).

In some embodiments, L² is absent.

In some embodiments, L² is a group of formula O.

In some embodiments, L² is a group of formula N(R^(N)).

In some embodiments, L² is a group of formula C(O).

In some embodiments, L³ is absent.

In some embodiments, L³ is a group of formula CH₂.

In some embodiments, L³ is a group of formula N(R^(N)).

In some embodiments, L³ is a group of formula C(O).

In some embodiments, L³ is a group of formula C≡C.

In some embodiments, Cy^(D71) is C₆₋₁₀ aryl (e.g., phenyl).

In some embodiments, Cy^(D71) is C₃₋₁₅ cycloalkyl (e.g., cyclopropyl).

In some embodiments, Cy^(D71) is 5-10 membered heteroaryl (e.g.,triazol, pyridine, dihydropyrido[2,1-b]pyrimidin-2-one,3,4-dihydroquinolin-2-one, benzo[d]isothiazole-1,1-dioxide, 2H-indazole,pyrazole, dioxolane, pyrrole, indole, imidazole, benzimidazole).

In some embodiments, Cy^(D71) is 4-10 membered heterocycloalkyl (e.g.,piperidine, 1,3-dioxolane, indoline, pyrrolidine).

In some embodiments, the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 memberedheteroaryl, or 4-10 membered heterocycloalkyl forming Cy^(D71) isunsubstituted.

In some embodiments, the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 memberedheteroaryl, or 4-10 membered heterocycloalkyl forming Cy^(D71) issubstituted.

In some embodiments, the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 memberedheteroaryl, or 4-10 membered heterocycloalkyl forming Cy^(D71) issubstituted by 1, 2, 3, 4 or 5 substituents each independently selectedfrom unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1), and C₁₋₆ alkyl or C₂₋₆ alkenyl that is substituted by1, 2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), C(O)OR^(a1), and NR^(c1)R^(d1).

In some embodiments, the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 memberedheteroaryl, or 4-10 membered heterocycloalkyl forming Cy^(D71) issubstituted by 0, 1 or 2 substituents selected from Cy^(D72),CH₂Cy^(D72), OCy^(D72), NHCy^(D72), O—C₁₋₆ alkylene-Cy^(D72), N(C₁₋₆alkyl)Cy^(D72), N(C(O)C₁₋₆ alkyl)Cy^(D72), and C(O)NHCy^(D72).

In some embodiments, Cy^(D72) is C₆₋₁₀ aryl (e.g., phenyl).

In some embodiments, Cy^(D72) is C₃₋₁₅ cycloalkyl (e.g., cyclopropyl).

In some embodiments, Cy^(D72) is 5-10 membered heteroaryl (e.g.,triazol, pyridine, dihydropyrido[2,1-b]pyrimidin-2-one,3,4-dihydroquinolin-2-one, benzo[d]isothiazole-1,1-dioxide, 2H-indazole,pyrazole, dioxolane, pyrrole, indole, imidazole, benzimidazole).

In some embodiments, Cy^(D72) is 4-10 membered heterocycloalkyl (e.g.,piperidine, 1,3-dioxolane, indoline, pyrrolidine).

In some embodiments, the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 memberedheteroaryl, or 4-10 membered heterocycloalkyl forming Cy^(D72) isunsubstituted.

In some embodiments, the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 memberedheteroaryl, or 4-10 membered heterocycloalkyl forming Cy^(D72) issubstituted.

In some embodiments, the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 memberedheteroaryl, or 4-10 membered heterocycloalkyl forming Cy^(D72) issubstituted by 0, 1 or 2 substituents selected from C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₁₅ cycloalkyl, halogen, C₁₋₆ haloalkyl, CN,OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), andC₁₋₆ alkyl that is substituted by 1, 2, or 3 substituents eachindependently selected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), C(O)OR^(a1), and NR^(c1)R^(d1).

In some embodiments, R¹ is H, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,Cy^(1A), OH, OC₁₋₆ alkyl, OCy^(1A), O(C₁₋₃ alkylenyl)Cy^(1A), NH₂,NHC₁₋₆ alkyl, N(C₁₋₆ alkyl)₂, NHCy^(1A), NH(C₁₋₃ alkylenyl)Cy^(1A),N(C₁₋₆ alkyl)Cy^(1A), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(1A).

In some embodiments, R¹ is Cy^(1A), OCy^(1A), O(C₁₋₃ alkylenyl)Cy^(1A),NHCy^(1A) NH(C₁₋₃ alkylenyl)Cy^(1A), N(C₁₋₆ alkyl)Cy^(1A), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(1A).

In some embodiments, R¹ is NHCy^(1A).

In some embodiments, R¹ is C₁₋₆ alkyl (e.g., methyl), C₂₋₆ alkenyl, C₂₋₆alkynyl, Cy^(1A)OH, or OC₁₋₆ alkyl (e.g., OMe).

In some embodiments, R¹ is OH.

In some embodiments, R¹ is a group of one of the following formulae:

wherein:

R¹¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and

R¹⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, R¹ is a group of one of the following formulae:

In some embodiments, Cy^(1A) is C₆₋₁₀ aryl, e.g., phenyl that isunsubstituted or substituted by 0, 1 or 2 Cy^(1B) and 0, 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1) and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, Cy^(1A) is C₆₋₁₀ aryl, e.g., phenyl that isunsubstituted or substituted by 1 Cy^(1B) and 0, 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1) and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, Cy^(1A) is C₆₋₁₀ aryl, e.g., phenyl that isunsubstituted or substituted by 1 Cy^(1B).

In some embodiments, each Cy^(1B) is C₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstitutedor substituted by 1, 2, 3, 4 or 5 substituents each independentlyselected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1) and C₁₋₆alkyl that is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1).

In some embodiments, each Cy^(1B) is unsubstituted C₃₋₁₅ cycloalkyl(e.g., C₃₋₁₀ cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl).

In some embodiments, Cy^(1A) is a group of one of the followingformulae:

wherein

R¹¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and

R¹⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, Cy^(1A) is a group of one of the followingformulae:

In some embodiments, Cy^(1A) is C₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstitutedor substituted by 0, 1 or 2 Cy^(1B) and 0, 1, 2, 3, 4 or 5 substituentseach independently selected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1),NR^(c1)R^(d1) and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1). In some embodiments, Cy^(1A) isC₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀ cycloalkyl, e.g., adamantyl, e.g.,adamant-1-yl) that is unsubstituted or substituted by 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1) and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1) In some embodiments, Cy^(1A) isunsubstituted C₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀ cycloalkyl, e.g., adamantyl,e.g., adamant-1-yl). In some embodiments, Cy^(1A) is adamantyl, e.g.,adamant-1-yl that is unsubstituted or substituted. In some embodiments,Cy^(1A) is unsubstituted adamantyl, e.g., adamant-1-yl.

In some embodiments:

-   -   R⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1) or        C₁₋₆ alkyl that is substituted by 1, 2, or 3 substituents each        independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), and NR^(c1)R^(d1); and    -   R⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1) or        C₁₋₆ alkyl that is substituted by 1, 2, or 3 substituents each        independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, R⁷ is H and R⁸ is H.

In some embodiments, L² is absent.

In some embodiments, L² is N(R^(N)).

In some embodiments, L² is C(O).

In some embodiments, R^(N) is H.

In some embodiments, A⁶ is CR⁶.

In some embodiments, R⁶ is H.

In some embodiments, A⁶ is N.

In some embodiments, A⁷ is CR⁷.

In some embodiments, R⁷ is H.

In some embodiments, R⁷ is Cy^(7A), OCy^(7A), O(C₁₋₃ alkylenyl)Cy^(7A),C(O)OCy^(7A), C(O)O(C₁₋₃ alkylenyl)Cy^(7A), NHCy^(7A), NH(C₁₋₃alkylenyl)Cy^(7A), N(C₁₋₆ alkyl)Cy^(7A), N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7A); C(O)NHCy^(7A), C(O)NH(C₁₋₃ alkylenyl)Cy^(7A),C(O)N(C₁₋₆ alkyl)Cy^(7A), or C(O)N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7A).

In some embodiments, R⁷ is Cy^(7A), OCy^(7A), O(C₁₋₃ alkylenyl)Cy^(7A),NHCy^(7A), NH(C₁₋₃ alkylenyl)Cy^(7A), N(C₁₋₆ alkyl)Cy^(7A), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(7A).

In some embodiments, R⁷ is N(C(O)C₁₋₆ alkyl)Cy^(7A).

In some embodiments, R⁷ is NHCy^(7A).

In some embodiments, R⁷ is a group of one of the following formulae:

wherein:

R⁷¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and

R⁷⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, R⁷ is a group of one of the following formulae:

In some embodiments, Cy^(7A) is C₆₋₁₀ aryl, e.g., phenyl that isunsubstituted or substituted by 0, 1 or 2 Cy^(7B) and 0, 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, Cy^(7A) is C₆₋₁₀ aryl, e.g., phenyl that isunsubstituted or substituted by 1 Cy^(7B) and 0, 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, Cy^(7A) is C₆₋₁₀ aryl, e.g., phenyl that isunsubstituted or substituted by 1 Cy^(7B).

In some embodiments, each Cy^(7B) is C₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstitutedor substituted by 1, 2, 3, 4 or 5 substituents each independentlyselected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), and C₁₋₆alkyl that is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1).

In some embodiments, each Cy^(7B) is unsubstituted C₃₋₁₅ cycloalkyl(e.g., C₃₋₁₀ cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl).

In some embodiments, Cy^(7A) is a group of one of the followingformulae:

wherein:

R⁷¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and

R⁷⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, Cy^(7A) is a group of one of the followingformulae:

In some embodiments, Cy^(7A) is C₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstitutedor substituted by 0, 1 or 2 Cy^(7B) and 0, 1, 2, 3, 4 or 5 substituentseach independently selected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1),NR^(c1)R^(d1) and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1). In some embodiments, Cy^(7A) isC₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀ cycloalkyl, e.g., adamantyl, e.g.,adamant-1-yl) that is unsubstituted or substituted by 01, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1) and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1) In some embodiments, Cy^(7A) isunsubstituted C₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀ cycloalkyl, e.g., adamantyl,e.g., adamant-1-yl). In some embodiments, Cy^(7A) is adamantyl, e.g.,adamant-1-yl that is unsubstituted or substituted. In some embodiments,Cy^(7A) is unsubstituted adamantyl, e.g., adamant-1-yl.

In some embodiments:

-   -   R¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1) or        C₁₋₆ alkyl that is substituted by 1, 2, or 3 substituents each        independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), and NR^(c1)R^(d1); and    -   R⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1) or        C₁₋₆ alkyl that is substituted by 1, 2, or 3 substituents each        independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, A¹ is CR¹, A² is CR², A³ is CR³, A⁴ is CR⁴, A⁵ isCR⁵, A⁶ is CR⁶, A⁸ is CR⁸, A⁹ is CR⁹, and A¹⁰ is CR¹⁰.

In some embodiments, A¹ is CR¹, A³ is CR³, A⁴ is CR⁴, A⁵ is N, A⁶ isCR⁶, A⁸ is CR⁸, A⁹ is CR⁹, and A¹⁰ is CR¹⁰.

In some embodiments, A⁷ is N.

In some embodiments, A⁸ is CR⁸.

In some embodiments, R⁸ is H.

In some embodiments, R⁸ is Cy^(8A), OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A),C(O)OCy^(8A), C(O)O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), C(O)NHCy^(8A), C(O)NH(C₁₋₃ alkylenyl)Cy^(8A),C(O)N(C₁₋₆ alkyl)Cy^(8A), or C(O)N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(8A).

In some embodiments, R⁸ is Cy^(8A), OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A),NHCy^(8A), NH(C₁₋₃ alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(8A).

In some embodiments, R⁸ is N(Cy^(8A))₂.

In some embodiments, R⁸ is N(C(O)C₁₋₆ alkyl)Cy^(8A).

In some embodiments, R⁸ is SO₂NHCy^(8A).

In some embodiments, R⁸ is C₁₋₃ alkylene-C(O)NHCy^(8A).

In some embodiments, R⁸ is NHCy^(8A).

In some embodiments, R⁸ is a group of one of the following formulae:

wherein:

R⁸¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and

R⁸⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, R⁸ is a group of one of the following formulae:

In some embodiments, Cy^(8A) is C₆₋₁₀ aryl, e.g., phenyl that isunsubstituted or substituted by 0, 1 or 2 Cy^(8B) and 0, 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1) and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, Cy^(8A) is C₆₋₁₀ aryl, e.g., phenyl that isunsubstituted or substituted by 1 Cy^(8B) and 0, 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, Cy^(8A) is C₆₋₁₀ aryl, e.g., phenyl that isunsubstituted or substituted by 1 Cy^(8B).

In some embodiments, each Cy^(8B) is C₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstitutedor substituted by 1, 2, 3, 4 or 5 substituents each independentlyselected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1) and C₁₋₆alkyl that is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1).

In some embodiments, each Cy^(8B) is unsubstituted C₃₋₁₅ cycloalkyl(e.g., C₃₋₁₀ cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl).

In some embodiments, Cy^(8A) is a group of one of the followingformulae:

wherein:

R⁸¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and

R⁸⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, Cy^(8A) is a group of one of the followingformulae:

In some embodiments, Cy^(8A) is C₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstitutedor substituted by 0, 1 or 2 Cy^(8B) and 0, 1, 2, 3, 4 or 5 substituentseach independently selected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1),NR^(c1)R^(d1) and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1). In some embodiments, Cy^(8A) isC₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀ cycloalkyl, e.g., adamantyl, e.g.,adamant-1-yl) that is unsubstituted or substituted by 01, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1) and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1) In some embodiments, Cy^(8A) isunsubstituted C₃₋₁₅ cycloalkyl (e.g., C₃₋₁₀ cycloalkyl, e.g., adamantyl,e.g., adamant-1-yl). In some embodiments, Cy^(8A) is adamantyl, e.g.,adamant-1-yl that is unsubstituted or substituted. In some embodiments,Cy^(8A) is unsubstituted adamantyl, e.g., adamant-1-yl.

In some embodiments:

-   -   R¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1) or        C₁₋₆ alkyl that is substituted by 1, 2, or 3 substituents each        independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), and NR^(c1)R^(d1); and    -   R⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,        halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1) or        C₁₋₆ alkyl that is substituted by 1, 2, or 3 substituents each        independently selected from halogen, C₁₋₆ haloalkyl, CN,        OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, A¹ is CR¹, A² is CR², A³ is CR³, A⁴ is CR⁴, A⁵ isCR⁵, A⁶ is CR⁶, A⁷ is CR⁷, A⁸ is CR⁸, A⁹ is CR⁹, and A¹⁰ is CR¹⁰.

In some embodiments, A¹ is CR¹, A³ is CR³, A⁴ is CR⁴, A⁵ is N, A⁶ isCR⁶, A⁷ is CR⁷, A⁸ is CR⁸, A⁹ is CR⁹, and A¹⁰ is CR¹⁰.

In some embodiments, A⁸ is N.

In some embodiments, A⁹ is CR⁹.

In some embodiments, R⁹ is H, C₁₋₆ alkyl or C₁₋₆ haloalkyl.

In some embodiments, R⁹ is H, methyl or trifluoroethyl.

In some embodiments, R⁹ is H.

In some embodiments, A⁹ is N.

In some embodiments, A¹⁰ is CR¹⁰.

In some embodiments, R¹⁰ is H.

In some embodiments, A¹⁰ is N.

In some embodiments, the compound is a compound of one of the followingformulae (I-1) to (I-60):

wherein:

R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R^(N), A¹, A², A³, A⁴, A⁵, A⁶,A⁷, A⁸, A⁹, A¹⁰, Cy^(1A), Cy^(1B), Cy^(7A), Cy^(7B), Cy^(8A), Cy^(8B),L¹ and L², are as defined above for the compounds of formula (I), or anyof the embodiments thereof;

L⁷ is absent, O, NH or N(C₁₋₆ alkyl);

L⁸ is absent, O, NH or N(C₁₋₆ alkyl);

R¹¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R¹⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH,OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁷⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and

R⁷⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH,OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);

R⁸⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and

R⁸⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH,OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1).

In some embodiments, R¹ is OH.

In some embodiments, R¹ is OC₁₋₆ alkyl (e.g., OMe).

In some embodiments, R¹ is C₂₋₆ alkenyl (e.g., vinyl).

In some embodiments, L⁷ is NH.

In some embodiments, L⁸ is NH.

In some embodiments, R^(a1), R^(b1), R^(c1) and R^(d1) are eachindependently selected from H, C₁₋₆ alkyl, HO—C₁₋₆ alkylene, C₁₋₆alkoxy-C₁₋₆ alkylene, C₆₋₁₀ aryl, C₂₋₆ alkenyl and C₂₋₆ alkynyl.

In some embodiments, the compound is a compound of one of the followingformulae, or a pharmaceutically acceptable salt thereof:

In some embodiments, the compound is a compound of one of the followingformulae, or a pharmaceutically acceptable salt thereof:

The compounds, or any of the embodiments thereof, can be provided in theform of a composition such as a pharmaceutical composition that includesthe compound, or a salt such as a pharmaceutically acceptable saltthereof, and at least one additional agent such as a pharmaceuticallyacceptable carrier.

It is further appreciated that certain features of the invention, whichare, for clarity, described in the context of separate embodiments, canalso be provided in combination in a single embodiment (while theembodiments are intended to be combined as if written in multiplydependent form). Conversely, various features of the invention whichare, for brevity, described in the context of a single embodiment, canalso be provided separately or in any suitable subcombination. Thus, itis contemplated that features described as embodiments of the compoundsof Formula (I) can be combined in any suitable combination.

At various places in the present specification, certain features of thecompounds are disclosed in groups or in ranges. It is specificallyintended that such a disclosure include each and every individualsubcombination of the members of such groups and ranges. For example,the term “C₁₋₆ alkyl” is specifically intended to individually disclose(without limitation) methyl, ethyl, C₃ alkyl, C₄ alkyl, C₅ alkyl and C₆alkyl.

The term “n-membered,” where n is an integer, typically describes thenumber of ring-forming atoms in a moiety where the number ofring-forming atoms is n. For example, piperidinyl is an example of a6-membered heterocycloalkyl ring, pyrazolyl is an example of a5-membered heteroaryl ring, pyridyl is an example of a 6-memberedheteroaryl ring and 1,2,3,4-tetrahydro-naphthalene is an example of a10-membered cycloalkyl group. When the term is used to refer to acarbocyclic ring (e.g., aryl or cycloalkyl), all of the ring atoms arecarbon atoms. When the term is used to refer to a heterocyclic ring(e.g., heteroaryl or heterocycloalkyl), one or more of the ring atoms(e.g., 1, 2, 3, or 4) are heteroatoms (e.g., nitrogen, oxygen or sulfur)and the remainder (e.g., n−1, n−2, n−3, or n−4) are carbon atoms.

At various places in the present specification, variables definingdivalent linking groups are described. It is specifically intended thateach linking substituent include both the forward and backward forms ofthe linking substituent. For example, —NR(CR′R″)_(n)— includes both—NR(CR′R″)_(n)— and —(CR′R″)_(n)NR— and is intended to disclose each ofthe forms individually. Where the structure requires a linking group,the Markush variables listed for that group are understood to be linkinggroups. For example, if the structure requires a linking group and theMarkush group definition for that variable lists “alkyl” or “aryl” thenit is understood that the “alkyl” or “aryl” represents a linkingalkylene group or arylene group, respectively.

The term “substituted” means that an atom or group of atoms formallyreplaces hydrogen as a “substituent” attached to another group. The term“substituted”, unless otherwise indicated, refers to any level ofsubstitution, e.g., mono-, di-, tri-, tetra- or penta-substitution,where such substitution is permitted. The substituents are independentlyselected, and substitution may be at any chemically accessible position.It is to be understood that substitution at a given atom is limited byvalency. The term “optionally substituted” means unsubstituted orsubstituted. The term “substituted” means that a hydrogen atom isremoved and replaced by a substituent. A single divalent substituent,e.g., oxo, can replace two hydrogen atoms.

The term “Cn-m” indicates a range which includes the endpoints, whereinn and m are integers and indicate the number of carbons. Examplesinclude C₁₋₄, C₁₋₆ and the like. Whenever the term is used intended todescribe each member included in the group, C_(n) through C_(m) as ifeach had been explicitly set forth. For example, the term C₁₋₆ isintended to describe each of the members C₁, C₂, C₃, C₄, C₅ and C₆.

The term “alkyl” employed alone or in combination with other terms,refers to a saturated hydrocarbon group that may be straight-chain orbranched. The term “Cn-m alkyl”, refers to an alkyl group having n to mcarbon atoms. An alkyl group formally corresponds to an alkane with oneC—H bond replaced by the point of attachment of the alkyl group to theremainder of the compound. In some embodiments, the alkyl group containsfrom 1 to 6 carbon atoms, from 1 to 4 carbon atoms, from 1 to 3 carbonatoms, or 1 to 2 carbon atoms. Examples of alkyl moieties include, butare not limited to, chemical groups such as methyl, ethyl, n-propyl,isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl; higher homologssuch as 2-methyl-1-butyl, n-pentyl, 3-pentyl, n-hexyl,1,2,2-trimethylpropyl and the like.

The term “alkenyl” employed alone or in combination with other terms,refers to a straight-chain or branched hydrocarbon group correspondingto an alkyl group having one or more double carbon-carbon bonds. Analkenyl group formally corresponds to an alkene with one C—H bondreplaced by the point of attachment of the alkenyl group to theremainder of the compound. The term “Cn-m alkenyl” refers to an alkenylgroup having n to m carbons. In some embodiments, the alkenyl moietycontains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. Example alkenyl groupsinclude, but are not limited to, ethenyl, n-propenyl, isopropenyl,n-butenyl, sec-butenyl and the like.

The term “alkynyl” employed alone or in combination with other terms,refers to a straight-chain or branched hydrocarbon group correspondingto an alkyl group having one or more triple carbon-carbon bonds. Analkynyl group formally corresponds to an alkyne with one C—H bondreplaced by the point of attachment of the alkyl group to the remainderof the compound. The term “Cn-m alkynyl” refers to an alkynyl grouphaving n to m carbons. Example alkynyl groups include, but are notlimited to, ethynyl, propyn-1-yl, propyn-2-yl and the like. In someembodiments, the alkynyl moiety contains 2 to 6, 2 to 4, or 2 to 3carbon atoms.

The term “alkylene”, employed alone or in combination with other terms,refers to a divalent alkyl linking group. An alkylene group formallycorresponds to an alkane with two C—H bond replaced by points ofattachment of the alkylene group to the remainder of the compound.

The term “Cn-m alkylene” refers to an alkylene group having n to mcarbon atoms. Examples of alkylene groups include, but are not limitedto, ethan-1,2-diyl, propan-1,3-diyl, propan-1,2-diyl, butan-1,4-diyl,butan-1,3-diyl, butan-1,2-diyl, 2-methyl-propan-1,3-diyl and the like.

The term “alkoxy”, employed alone or in combination with other terms,refers to a group of formula —O-alkyl, wherein the alkyl group is asdefined above. The term “Cn-m alkoxy” refers to an alkoxy group, thealkyl group of which has n to m carbons. Example alkoxy groups includemethoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), t-butoxy andthe like. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1to 3 carbon atoms.

The terms “halo” or “halogen”, used alone or in combination with otherterms, refers to fluoro, chloro, bromo and iodo.

The term “haloalkyl” refers to an alkyl group in which one or more ofthe hydrogen atoms has been replaced by a halogen atom. The term“C_(n-m) haloalkyl” refers to a C_(n-m) alkyl group having n to m carbonatoms and from at least one up to {2(n to m)+1} halogen atoms, which mayeither be the same or different. In some embodiments, the halogen atomsare fluoro atoms. In some embodiments, the haloalkyl group has 1 to 6 or1 to 4 carbon atoms. Example haloalkyl groups include CF₃, C₂F₅, CHF₂,CCl₃, CHCl₂, C₂Cl₅ and the like. In some embodiments, the haloalkylgroup is a fluoroalkyl group.

The term “haloalkoxy”, employed alone or in combination with otherterms, refers to a group of formula —O-haloalkyl, wherein the haloalkylgroup is as defined above. The term “C_(n-m) haloalkoxy” refers to ahaloalkoxy group, the haloalkyl group of which has n to m carbons.Example haloalkoxy groups include trifluoromethoxy and the like. In someembodiments, the haloalkoxy group has 1 to 6, 1 to 4, or 1 to 3 carbonatoms.

The term “amino” refers to a group of formula —NH₂.

The term “carbamyl” refers to a group of formula —C(═O)NH₂.

The term “carbonyl”, employed alone or in combination with other terms,refers to a —C(═O)— group, which also may be written as C(O).

The term “carbonyl”, employed alone or in combination with other terms,refers to a —C(═O)— group.

The term “carboxy” refers to a group of formula —C(═O)OH.

The term “oxo” refers to oxygen as a divalent substituent, forming acarbonyl group, or attached to a heteroatom forming a sulfoxide orsulfone group, or an N-oxide group.

The term “aromatic” refers to a carbocycle or heterocycle having one ormore polyunsaturated rings having aromatic character (i.e., having(4n+2) delocalized 7r (pi) electrons where n is an integer).

The term “aryl,” employed alone or in combination with other terms,refers to an aromatic hydrocarbon group, which may be monocyclic orpolycyclic (e.g., having 2, 3 or 4 fused rings). The term “Cn-m aryl”refers to an aryl group having from n to m ring carbon atoms. Arylgroups include, e.g., phenyl, naphthyl, indenyl and the like. In someembodiments, aryl groups have from 6 to 10 carbon atoms. In someembodiments, the aryl group is phenyl.

The term “arylalkylenyl,” employed alone or in combination with otherterms, refers to an aryl group, as defined herein, attached to analkylene group, as defined herein. The term “C_(n-m) aryl C_(o-p)alkylenyl” refers to an arylalkylenyl group with an aryl group havingfrom n to m ring carbon atoms attached to an alkylene group having fromo to p carbon atoms. Arylalkylenyl groups include, e.g., benzyl,phenethyl and the like.

The term “heteroaryl” or “heteroaromatic” employed alone or incombination with other terms, refers to a monocyclic or polycyclicaromatic heterocycle having at least one heteroatom ring member selectedfrom sulfur, oxygen and nitrogen. In some embodiments, the heteroaryl isa 5- or 6-membered monocyclic heteroaryl ring. In some embodiments, theheteroaryl is 5- to 10-membered C₁₋₉ heteroaryl, which is monocyclic orbicyclic and which has 1, 2, 3 or 4 heteroatom ring membersindependently selected from nitrogen, sulfur and oxygen. In someembodiments, any ring-forming N in a heteroaryl moiety can be anN-oxide. In some embodiments, the heteroaryl has 5-10 ring atomsincluding carbon atoms and 1, 2, 3 or 4 heteroatom ring membersindependently selected from nitrogen, sulfur and oxygen. In someembodiments, the heteroaryl has 5-6 ring atoms and 1, 2, 3, or 4heteroatom ring members independently selected from nitrogen, sulfur andoxygen. In some embodiments, the heteroaryl has 5-6 ring atoms and 1 or2 heteroatom ring members independently selected from nitrogen, sulfurand oxygen. In some embodiments, the heteroaryl is a five-membered orsix-membered heteroaryl ring. Example heteroaryl groups include, but arenot limited to, pyridine, pyrimidine, pyrazine, pyridazine, pyrrole,pyrazole, azolyl, oxazole, thiazole, imidazole, furan, thiophene,quinoline, isoquinoline, indole, benzothiophene, benzofuran,benzisoxazole, imidazo[1,2-b]thiazole, imidazo[1,2-b]pyridazine, purine,furopyridine (e.g., furo[3,2-b]pyridine), thienopyridine (e.g.thieno[3,2-b]pyridine) or the like.

A five-membered heteroaryl ring is a heteroaryl group having five ringatoms wherein one or more (e.g., 1, 2, 3 or 4) ring atoms areindependently selected from N, O and S. Exemplary five-membered ringheteroaryls include thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl,oxazolyl, pyrazolyl, isothiazolyl, isoxazolyl, 1,2,3-triazolyl,tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-triazolyl,1,2,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-triazolyl,1,3,4-thiadiazolyl and 1,3,4-oxadiazolyl.

A six-membered heteroaryl ring is a heteroaryl group having six ringatoms wherein one or more (e.g., 1, 2 or 3) ring atoms are independentlyselected from N, O and S. Exemplary six-membered ring heteroaryls arepyridyl, pyrazinyl, pyrimidinyl, triazinyl and pyridazinyl.

The term “heteroarylalkylenyl,” employed alone or in combination withother terms, refers to heteroaryl group, as defined herein, attached toan alkylene group, as defined herein. The term “n-m membered heteroarylC_(o-p) alkylenyl” refers to a heteroaryl group having from n to m ringatoms attached to an alkylene group having from o to p carbon atoms.Heteroarylalkylenyl groups include, e.g., pyridylmethyl, pyridylethyland the like.

The term “cycloalkyl”, employed alone or in combination with otherterms, refers to a non-aromatic, saturated, monocyclic, bicyclic orpolycyclic hydrocarbon ring system, including cyclized alkyl and alkenylgroups. The term “Cn-m cycloalkyl” refers to a cycloalkyl that has n tom ring member carbon atoms. Cycloalkyl groups can include mono- orpolycyclic (e.g., having 2, 3 or 4 fused rings) groups and spirocycles.Cycloalkyl groups can have, e.g., 3, 4, 5, 6, 7, 8, 9 or 10 ring-formingcarbons (C₃₋₁₀) or 3, 4, 5, 6 or 7 ring-forming carbons (C₃₋₇). In someembodiments, the cycloalkyl group has 3 to 6 ring members, 3 to 5 ringmembers, or 3 to 4 ring members. In some embodiments, the cycloalkylgroup is monocyclic. In some embodiments, the cycloalkyl group ismonocyclic or bicyclic. In some embodiments, the cycloalkyl group is aC₃₋₆ monocyclic cycloalkyl group. Ring-forming carbon atoms of acycloalkyl group can be optionally substituted by oxo or sulfido.Cycloalkyl groups also include cycloalkylidenes. Example cycloalkylgroups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cyclopentenyl, cyclohexenyl, cyclohexadienyl, norbornyl, norpinyl,bicyclo[2.1.1]hexanyl, bicyclo[1.1.1]pentanyl, adamantyl and the like.In some embodiments, cycloalkyl is cyclopropyl, cyclobutyl, cyclopentylor cyclohexyl. Also included in the definition of cycloalkyl aremoieties that have one or more aromatic rings fused (i.e., having a bondin common with) to the cycloalkyl ring, e.g., benzo or thienylderivatives of cyclopentane, cyclohexane and the like, for exampleindanyl or tetrahydronaphthyl. A cycloalkyl group containing a fusedaromatic ring can be attached through any ring-forming atom including aring-forming atom of the fused aromatic ring.

The term “arylalkylenyl,” employed alone or in combination with otherterms, refers to a cycloalkyl group, as defined herein, attached to analkylene group, as defined herein. The term “Cn-m cycloalkyl C_(o-p)alkylenyl” refers to an cycloalkylalkylenyl group with a cycloalkylgroup having from n to m ring carbon atoms attached to an alkylene grouphaving from o to p carbon atoms. Cycloalkylalkylenyl groups include,e.g., cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl,cyclohexylmethyl, and the like.

The term “heterocycloalkyl”, employed alone or in combination with otherterms, refers to non-aromatic ring or ring system, which may optionallycontain one or more alkenylene groups as part of the ring structure,which has at least one heteroatom ring member independently selectedfrom nitrogen, sulfur oxygen and phosphorus, and which has 4-10 ringmembers, 4-7 ring members or 4-6 ring members. Included inheterocycloalkyl are monocyclic 4-, 5-, 6- and 7-memberedheterocycloalkyl groups. Heterocycloalkyl groups can include mono- orbicyclic (e.g., having two fused or bridged rings) ring systems. In someembodiments, the heterocycloalkyl group is a monocyclic group having 1,2 or 3 heteroatoms independently selected from nitrogen, sulfur andoxygen. Examples of heterocycloalkyl groups include azetidine,pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, pyran,azepane, tetrahydropyran, tetrahydrofuran, dihydropyran, dihydrofuranand the like. Ring-forming carbon atoms and heteroatoms of aheterocycloalkyl group can be optionally substituted by oxo or sulfido(e.g., C(═O), S(═O), C(S) or S(═O)₂, etc.) or a nitrogen atom can bequaternized. The heterocycloalkyl group can be attached through aring-forming carbon atom or a ring-forming heteroatom. In someembodiments, the heterocycloalkyl group contains 0 to 3 double bonds. Insome embodiments, the heterocycloalkyl group contains 0 to 2 doublebonds. Also included in the definition of heterocycloalkyl are moietiesthat have one or more aromatic rings fused (i.e., having a bond incommon with) to the heterocycloalkyl ring, e.g., benzo or thienylderivatives of piperidine, morpholine, azepine, etc. A heterocycloalkylgroup containing a fused aromatic ring can be attached through anyring-forming atom including a ring-forming atom of the fused aromaticring. Examples of heterocycloalkyl groups include 1, 2, 3,4-tetrahydroquinoline, dihydrobenzofuran, azetidine, azepane, diazepan(e.g., 1,4-diazepan), pyrrolidine, piperidine, piperazine, morpholine,thiomorpholine, pyran, tetrahydrofuran and di- and tetra-hydropyran.

The term “heterocycloalkylalkylenyl,” employed alone or in combinationwith other terms, refers to heterocycloalkyl group, as defined herein,attached to an alkylene group, as defined herein. The term “n-m memberedheterocycloalkyl C_(o-p) alkylenyl” refers to a heterocycloalkyl grouphaving from n to m ring atoms attached to an alkylene group having fromo to p carbon atoms. Heteroarylalkylenyl groups include, e.g.,tetrahydrofurylmethyl.

At certain places, the definitions or embodiments refer to specificrings (e.g., an azetidine ring, a pyridine ring, etc.). Unless otherwiseindicated, these rings can be attached to any ring member provided thatthe valency of the atom is not exceeded. For example, an azetidine ringmay be attached at any position of the ring, whereas an azetidin-3-ylring is attached at the 3-position.

The compounds described herein can be asymmetric (e.g., having one ormore stereocenters). All stereoisomers, such as enantiomers anddiastereoisomers, are intended unless otherwise indicated. Compounds ofthe present invention that contain asymmetrically substituted carbonatoms can be isolated in optically active or racemic forms. Methods onhow to prepare optically active forms from optically inactive startingmaterials are known in the art, such as by resolution of racemicmixtures or by stereoselective synthesis. Many geometric isomers ofolefins, C═N double bonds and the like can also be present in thecompounds described herein, and all such stable isomers are contemplatedin the present invention. Cis and trans geometric isomers of thecompounds of the present invention are described and may be isolated asa mixture of isomers or as separated isomeric forms.

Resolution of racemic mixtures of compounds can be carried out by any ofnumerous methods known in the art. One method includes fractionalrecrystallization using a chiral resolving acid which is an opticallyactive, salt-forming organic acid. Suitable resolving agents forfractional recrystallization methods are, e.g., optically active acids,such as the D and L forms of tartaric acid, diacetyltartaric acid,dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid or thevarious optically active camphorsulfonic acids such as β-camphorsulfonicacid. Other resolving agents suitable for fractional crystallizationmethods include stereoisomerically pure forms of α-methylbenzylamine(e.g., S and R forms, or diastereoisomerically pure forms),2-phenylglycinol, norephedrine, ephedrine, N-methylephedrine,cyclohexylethylamine, 1,2-diaminocyclohexane and the like.

Resolution of racemic mixtures can also be carried out by elution on acolumn packed with an optically active resolving agent (e.g.,dinitrobenzoylphenylglycine). Suitable elution solvent composition canbe determined by one skilled in the art.

In some embodiments, the compounds of the invention have the(R)-configuration. In other embodiments, the compounds have the(S)-configuration. In compounds with more than one chiral centers, eachof the chiral centers in the compound may be independently (R) or (S),unless otherwise indicated.

Compounds of the invention also include tautomeric forms. Tautomericforms result from the swapping of a single bond with an adjacent doublebond together with the concomitant migration of a proton. Tautomericforms include prototropic tautomers which are isomeric protonationstates having the same empirical formula and total charge. Exampleprototropic tautomers include ketone-enol pairs, amide-imidic acidpairs, lactam-lactim pairs, enamine-imine pairs, and annular forms wherea proton can occupy two or more positions of a heterocyclic system,e.g., 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and2H-isoindole and 1H- and 2H-pyrazole. Tautomeric forms can be inequilibrium or sterically locked into one form by appropriatesubstitution.

Compounds of the invention can also include all isotopes of atomsoccurring in the intermediates or final compounds. Isotopes includethose atoms having the same atomic number but different mass numbers.For example, isotopes of hydrogen include tritium and deuterium.

The term, “compound,” is meant to include all stereoisomers, geometricisomers, tautomers and isotopes of the structures depicted.

All compounds, and pharmaceutically acceptable salts thereof, can befound together with other substances such as water and solvents (e.g.,hydrates and solvates) or can be isolated. When in the solid state, thecompounds described herein and salts thereof may occur in various formsand may, e.g., take the form of solvates, including hydrates. Thecompounds may be in any solid state form, such as a polymorph orsolvate, so unless clearly indicated otherwise, reference in thespecification to compounds and salts thereof should be understood asencompassing any solid state form of the compound.

In some embodiments, the compounds of the invention, or salts thereof,are substantially isolated. By “substantially isolated” is meant thatthe compound is at least partially or substantially separated from theenvironment in which it was formed or detected. Partial separation caninclude, e.g., a composition enriched in the compounds of the invention.Substantial separation can include compositions containing at leastabout 50%, at least about 60%, at least about 70%, at least about 80%,at least about 90%, at least about 95%, at least about 97%, or at leastabout 99% by weight of the compounds of the invention, or salt thereof.

The phrase “pharmaceutically acceptable” is employed herein to refer tothose compounds, materials, compositions and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of human beings and animals without excessive toxicity,irritation, allergic response, or other problem or complication,commensurate with a reasonable benefit/risk ratio.

The expressions, “ambient temperature” and “room temperature” areunderstood in the art, and refer generally to a temperature, e.g., areaction temperature, that is about the temperature of the room in whichthe reaction is carried out, e.g., a temperature from about 20° C. toabout 30° C.

The present invention also includes salts, particularly pharmaceuticallyacceptable salts, of the compounds described herein. The term“pharmaceutically acceptable salts” refers to derivatives of thedisclosed compounds wherein the parent compound is modified byconverting an existing acid or base moiety to its salt form. Examples ofpharmaceutically acceptable salts include, but are not limited to,mineral or organic acid salts of basic residues such as amines; alkalior organic salts of acidic residues such as carboxylic acids; and thelike. The pharmaceutically acceptable salts of the present inventioninclude the non-toxic salts of the parent compound formed, e.g., fromnon-toxic inorganic or organic acids. The pharmaceutically acceptablesalts of the present invention can be synthesized from the parentcompound which contains a basic or acidic moiety by conventionalchemical methods. Generally, such salts can be prepared by reacting thefree acid or base forms of these compounds with a stoichiometric amountof the appropriate base or acid in water or in an organic solvent, or ina mixture of the two; generally, non-aqueous media like ether, ethylacetate, alcohols (e.g., methanol, ethanol, iso-propanol or butanol) oracetonitrile (MeCN) are preferred. Lists of suitable salts are found inRemington's Pharmaceutical Sciences, 17^(th) Ed., (Mack PublishingCompany, Easton, 1985), p. 1418, Berge et al., J. Pharm. Sci., 1977,66(1), 1-19 and in Stahl et al., Handbook of Pharmaceutical Salts:Properties, Selection, and Use, (Wiley, 2002). In some embodiments, thecompounds described herein include the N-oxide forms.

The following abbreviations may be used herein: AcOH (acetic acid); Ac₂O(acetic anhydride); Al₂O₃ (aluminium oxide); aq. (aqueous); atm.(atmosphere(s)); Boc (t-butoxycarbonyl); Boc₂O(di-tert-butyldicarbonate); BOP((benzotriazol-1-yloxy)tris(dimethylamino)phosphoniumhexafluorophosphate); br (broad); c-Pr (cyclopropyl); Cbz(carboxybenzyl); calc. (calculated); CeCl₃.7H₂O (cerium (III) chlorideheptahydrate); Cs₂CO₃ (cesium carbonate); CuI (copper (I) iodide); d(doublet); dd (doublet of doublets); DCM (dichloromethane); DIPEA(N,N-diisopropylethylamine); DMAP (4-dimethylaminopyridine); DMF(N,N-dimethylformamide); DMSO (dimethylsulfoxide); Et (ethyl); EtOAc(ethyl acetate); EtOH (ethanol); Fmoc(9-fluorenylmethylmethoxycarbonyl); g (gram(s)); h (hour(s)); H₂(hydrogen gas); H₂O₂ (hydrogen peroxide); HATU(N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uroniumhexafluorophosphate); HBr (hydrogen bromide); HCl (hydrochloric acid orhydrogen chloride); HPLC (high performance liquid chromatography); Hz(hertz); i-Pr (isopropyl); i-PrOH (isopropyl alcohol); J (couplingconstant); KOAc (potassium acetate); K₃PO₄ (potassium phosphate);K₃PO₄.H₂O (tripotassium phosphate hydrate); LCMS (liquidchromatography-mass spectrometry); LiAlH₄ (lithium tetrahydroaluminate);LiBH₄ (lithium tetrahydroborate); LiOH (lithium hydroxide); LiOH.H₂O(lithium hydroxide monohydrate); m (multiplet); M (molar); mCPBA(m-chloroperbenzoic acid); Me (methyl); MeCN (acetonitrile); MeOH(methanol); MgSO₄ (magnesium sulfate); MS (mass spectrometry); mg(milligram(s)); min. (minutes(s)); mL (milliliter(s)); mmol(millimole(s)); N (normal); N₂ (nitrogen gas); NaHCO₃ (sodiumbicarbonate); NaIO₄ (sodium metaperiodate); NaN₃ (sodium azide); NaOH(sodium hydroxide); Na₂SO₄ (sodium sulfate); n-Bu (n-butyl); n-BuLi(n-butyllithium); NH₄Cl (ammonium chloride); NH₄OH (ammonium hydroxide);nM (nanomolar); NMR (nuclear magnetic resonance spectroscopy); Pd(palladium); Pd(dppf)Cl₂([1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride);Pd(OAc)₂ (palladium acetate); Pd(tBu₃P)₂(bis(tri-tert-butylphosphine)palladium); pM (picomolar); Pd(PPh₃)₄(tetrakis(triphenylphosphine)palladium(O)); PPh₃ (triphenylphosphine);psi (pounds per square inch); PTFE (polytetrafluoroethylene); RP-HPLC(reverse phase high performance liquid chromatography); r.t. (roomtemperature); s (singlet); t (triplet or tertiary); tert (tertiary); tt(triplet of triplets); TBAF (tetra-n-butylammoniumfluoride); t-Bu(tert-butyl); TEA (triethylamine); TFA (trifluoroacetic acid); THF(tetrahydrofuran); μg (microgram(s)); μL (microliter(s)); m(micromolar); wt % (weight percent).

II. SYNTHESIS

Compounds of the invention, including salts thereof, can be preparedusing known organic synthesis techniques and can be synthesizedaccording to any of numerous possible synthetic routes, such as shown inthe Scheme below.

The reactions for preparing compounds of the invention can be carriedout in suitable solvents which can be readily selected by one of skillin the art of organic synthesis. Suitable solvents can be substantiallynon-reactive with the starting materials (reactants), the intermediatesor products at the temperatures at which the reactions are carried out,e.g., temperatures which can range from the solvent's freezingtemperature to the solvent's boiling temperature. A given reaction canbe carried out in one solvent or a mixture of more than one solvent.Depending on the particular reaction step, suitable solvents for aparticular reaction step can be selected by the skilled artisan.

Preparation of compounds of the invention can involve the protection anddeprotection of various chemical groups. The need for protection anddeprotection, and the selection of appropriate protecting groups, can bereadily determined by one skilled in the art. The chemistry ofprotecting groups is described, e.g., in Kocienski, Protecting Groups,(Thieme, 2007); Robertson, Protecting Group Chemistry, (OxfordUniversity Press, 2000); Smith et al., March's Advanced OrganicChemistry: Reactions, Mechanisms, and Structure, 6^(th) Ed. (Wiley,2007); Peturssion et al., “Protecting Groups in Carbohydrate Chemistry,”J. Chem. Educ., 1997, 74(11), 1297; and Wuts et al., Protective Groupsin Organic Synthesis, 4th Ed., (Wiley, 2006).

Reactions can be monitored according to any suitable method known in theart. For example, product formation can be monitored by spectroscopicmeans, such as nuclear magnetic resonance spectroscopy (e.g., ¹H or¹³C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), massspectrometry or by chromatographic methods such as high performanceliquid chromatography (HPLC) or thin layer chromatography (TLC).

The Schemes below provide general guidance in connection with preparingthe compounds of the invention. One skilled in the art would understandthat the preparations shown in the Schemes can be modified or optimizedusing general knowledge of organic chemistry to prepare variouscompounds of the invention.

Compounds of Formula (I) can be prepared as shown in Scheme 1 bycoupling an aniline of Formula (II) with a compound of formula III,wherein L is a suitable leaving group, which can include halogen, suchas bromine or iodine, or a sulfonate group (alkyl or aryl sulfonate,such as methanesulfonate, trifluoromethanesulfonate, benzenesulfonate,p-toluenesulfonate, or naphthalenesulfonate). The reaction can becarried out in the presence of a base such as potassium carbonate and acopper salt such as copper (I) iodide or copper (I) oxide. The reactioncan also be carried out in the presence of a suitable organometalliccatalyst, e.g., using Buchwald-Hartwig cross-coupling conditions.Suitable solvents for the reaction include tetrahydrofuran, 1,4-dioxane,tolune, or 1,2-dichlorobenzene. The preferred solvent is1,2-dichlorobenzene. The reaction can typically be performed at atemperature of 0-200° C., e.g., a temperature of 100-150° C.

The present disclosure provides, inter alia, a methods of making certaincompounds of Formula (I) according to Formula (Ia) by the route shown inScheme 1:

Compounds of Formula (II) and (III) are either commercially available,known in the literature, or may be prepared by methods known to oneskilled in the art.

Certain compounds of formula (I) may be useful as intermediates in thesynthesis of other compounds of formula (I). For example, compounds offormula (I) wherein R¹ is OC₁₋₆ alkyl, OCy^(1A), O(C₁₋₃alkylenyl)Cy^(1A), NHCy^(1A) NH(C₁₋₃ alkylenyl)Cy^(1A), N(C₁₋₆alkyl)Cy^(1A), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(1A) can be used tosynthesize compounds of formula (I) wherein R¹ is OH via hydrolysis ofthe ester or amide group.

It will be appreciated by one skilled in the art that the processesdescribed are not the exclusive means by which compounds of theinvention may be synthesized and that a broad repertoire of syntheticorganic reactions is available to be potentially employed insynthesizing compounds of the invention. The person skilled in the artknows how to select and implement appropriate synthetic routes. Suitablesynthetic methods of starting materials, intermediates and products maybe identified by reference to the literature, including referencesources such as: Advances in Heterocyclic Chemistry, Vols. 1-107(Elsevier, 1963-2012); Journal of Heterocyclic Chemistry Vols. 1-49(Journal of Heterocyclic Chemistry, 1964-2012); Carreira, et al. (Ed.)Science of Synthesis, Vols. 1-48 (2001-2010) and Knowledge UpdatesKU2010/1-4; 2011/1-4; 2012/1-2 (Thieme, 2001-2012); Katritzky, et al.(Ed.) Comprehensive Organic Functional Group Transformations, (PergamonPress, 1996); Katritzky et al. (Ed.); Comprehensive Organic FunctionalGroup Transformations II (Elsevier, 2^(nd) Edition, 2004); Katritzky etal. (Ed.), Comprehensive Heterocyclic Chemistry (Pergamon Press, 1984);Katritzky et al., Comprehensive Heterocyclic Chemistry II, (PergamonPress, 1996); Smith et al., March's Advanced Organic Chemistry:Reactions, Mechanisms, and Structure, 6^(th) Ed. (Wiley, 2007); Trost etal. (Ed.), Comprehensive Organic Synthesis (Pergamon Press, 1991).

III. USES OF THE COMPOUNDS

Compounds of the invention can inhibit the autopalmitoylation ofTEAD-transcription factors and, thus, are useful in treating diseasesand disorders associated with activity of TEAD-transcription factors.For the uses described herein, any of the compounds of the invention,including any of the embodiments thereof, may be used.

Thus, the present disclosure provides methods of treating aTEAD-transcription factor-associated disease or disorder in anindividual (e.g., patient) by administering to the individual in need ofsuch treatment a therapeutically effective amount or dose of a compoundof Formula (I), or any of the embodiments thereof, or a pharmaceuticalcomposition thereof. The present disclosure also provides a compound ofFormula (I), or any of the embodiments thereof, or a pharmaceuticalcomposition thereof, for use in treating a TEAD-transcription factorassociated disease or disorder. Also provided is the use of a compoundof Formula (I), or any of the embodiments thereof, or a pharmaceuticalcomposition thereof, in the manufacture of a medicament for treating aTEAD-transcription factor-associated disease or disorder. The disease ordisorder can be one that is associated with TEAD1, TEAD2, TEAD3, orTEAD4.

A TEAD-transcription factor-associated disease can include any disease,disorder or condition that is directly or indirectly linked toexpression or activity of TEAD-transcription factors, includingover-expression and/or abnormal activity levels. Abnormal activitylevels can be determined by comparing activity level in normal, healthytissue or cells with activity level in diseased cells. ATEAD-transcription factor-associated disease can also include anydisease, disorder or condition that can be prevented, ameliorated,inhibited or cured by modulating TEAD-transcription factor activity. Insome embodiments, the disease is characterized by the abnormal activityor expression (e.g., overexpression) of TEAD-transcription factor. ATEAD-transcription factor-associated disease can also refer to anydisease, disorder or condition wherein modulating the expression oractivity TEAD-transcription factor is beneficial.

TEAD-transcription factor associated diseases that can be treated usingthe compounds of the invention include cancer. The cancers include solidtumors, e.g., prostate cancer, colon cancer, esophageal cancer,endometrial cancer, ovarian cancer, uterine cancer, renal cancer,hepatic cancer, pancreatic cancer, gastric cancer, breast cancer, lungcancer, cancers of the head or neck, thyroid cancer, glioblastoma,sarcoma, bladder cancer, etc. Other TEAD-transcription factor associateddiseases include hepatocellular carcinoma, medulloblastoma, cutaneoussquamous cell carcinoma, lung cancer, pancreatic cancer, esophaguscancer, liver cancer, colon cancer, melanoma, or uveal melanoma.TEAD-transcription factor associated diseases also include hematologicalcancers, e.g., lymphoma, leukemia such as acute lymphoblastic leukemia(ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia(CLL), chronic myelogenous leukemia (CML), diffuse large B-cell lymphoma(DLBCL), mantle cell lymphoma, non-Hodgkin lymphoma (including relapsednon-Hodgkin lymphoma, refractory non-Hodgkin lymphoma and recurrentfollicular non-Hodgkin lymphoma), Hodgkin lymphoma and multiple myeloma.

The cancer can be a cancer in which abnormally proliferating cells ofthe cancer express one or more TEADs, for example, a cancer thatexpresses one or more of TEAD1, TEAD2, TEAD3, and/or TEAD4. The methodcan include testing cancer cells of the individual for expression of oneor more TEADs, e.g., one or more of TEAD1, TEAD2, TEAD3, and/or TEAD4,and treating the cancer according to the methods described herein basedon the determination that the cancer expresses TEAD1, TEAD2, TEAD3,and/or TEAD4.

The terms “individual” or “patient,” used interchangeably, refer to anyanimal, including mammals, preferably mice, rats, other rodents,rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and mostpreferably humans.

The phrase “therapeutically effective amount” refers to the amount ofactive compound or pharmaceutical agent that elicits the biological ormedicinal response in a tissue, system, animal, individual or human thatis being sought by a researcher, veterinarian, medical doctor or otherclinician.

The term “treating” or “treatment” refers to one or more of (1)inhibiting the disease; e.g., inhibiting a disease, condition ordisorder in an individual who is experiencing or displaying thepathology or symptomatology of the disease, condition or disorder (i.e.,arresting further development of the pathology and/or symptomatology);and (2) ameliorating the disease; e.g., ameliorating a disease,condition or disorder in an individual who is experiencing or displayingthe pathology or symptomatology of the disease, condition or disorder(i.e., reversing the pathology and/or symptomatology) such as decreasingthe severity of disease. In one embodiment, treating or treatmentincludes preventing or reducing the risk of developing the disease;e.g., preventing or reducing the risk of developing a disease, conditionor disorder in an individual who may be predisposed to the disease,condition or disorder but does not yet experience or display thepathology or symptomatology of the disease.

Combination Therapies

Cancer cell growth and survival can be impacted by multiple signalingpathways. Thus, it is useful to combine different chemotherapeuticagents treat such conditions. Use of combination therapy may reduce thelikelihood of drug-resistance arising in a cell population, and/orreduce the toxicity of treatment.

The compounds can be administered in combination with one or moreanti-cancer drugs, such as a chemotherapeutics. Examplechemotherapeutics include any of: abarelix, aldesleukin, alemtuzumab,alitretinoin, allopurinol, altretamine, anastrozole, arsenic trioxide,asparaginase, azacitidine, bevacizumab, bexarotene, bleomycin,bortezombi, bortezomib, busulfan intravenous, busulfan oral,calusterone, capecitabine, carboplatin, carmustine, cetuximab,chlorambucil, cisplatin, cladribine, clofarabine, cyclophosphamide,cytarabine, dacarbazine, dactinomycin, dalteparin sodium, dasatinib,daunorubicin, decitabine, denileukin, denileukin diftitox, dexrazoxane,docetaxel, doxorubicin, dromostanolone propionate, eculizumab,epirubicin, erlotinib, estramustine, etoposide phosphate, etoposide,exemestane, fentanyl citrate, filgrastim, floxuridine, fludarabine,fluorouracil, fulvestrant, gefitinib, gemcitabine, gemtuzumabozogamicin, goserelin acetate, histrelin acetate, ibritumomab tiuxetan,idarubicin, ifosfamide, imatinib mesylate, interferon alfa 2a,irinotecan, lapatinib ditosylate, lenalidomide, letrozole, leucovorin,leuprolide acetate, levamisole, lomustine, meclorethamine, megestrolacetate, melphalan, mercaptopurine, methotrexate, methoxsalen, mitomycinC, mitotane, mitoxantrone, nandrolone phenpropionate, nelarabine,nofetumomab, oxaliplatin, paclitaxel, pamidronate, panitumumab,pegaspargase, pegfilgrastim, pemetrexed disodium, pentostatin,pipobroman, plicamycin, procarbazine, quinacrine, rasburicase,rituximab, ruxolitinib, sorafenib, streptozocin, sunitinib, sunitinibmaleate, tamoxifen, temozolomide, teniposide, testolactone, thalidomide,thioguanine, thiotepa, topotecan, toremifene, tositumomab, trastuzumab,tretinoin, uracil mustard, valrubicin, vinblastine, vincristine,vinorelbine, vorinostat and zoledronate.

When more than one pharmaceutical agent is administered to a patient,they can be administered simultaneously, sequentially, or in combination(e.g., for more than two agents).

VI. Formulation, Dosage Forms and Administration

When employed as pharmaceuticals, the compounds of the invention can beadministered in the form of pharmaceutical compositions. Thus thepresent disclosure provides a composition comprising a compound Formula(I), or a pharmaceutically acceptable salt thereof, or any of theembodiments thereof, and at least one pharmaceutically acceptablecarrier. These compositions can be prepared in a manner well known inthe pharmaceutical art, and can be administered by a variety of routes,depending upon whether local or systemic treatment is indicated and uponthe area to be treated. Administration may be topical (includingtransdermal, epidermal, ophthalmic and to mucous membranes includingintranasal, vaginal and rectal delivery), pulmonary (e.g., by inhalationor insufflation of powders or aerosols, including by nebulizer;intratracheal or intranasal), oral or parenteral. Parenteraladministration includes intravenous, intraarterial, subcutaneous,intraperitoneal intramuscular or injection or infusion; or intracranial,e.g., intrathecal or intraventricular, administration. Parenteraladministration can be in the form of a single bolus dose, or may be,e.g., by a continuous perfusion pump. Pharmaceutical compositions andformulations for topical administration may include transdermal patches,ointments, lotions, creams, gels, drops, suppositories, sprays, liquidsand powders. Conventional pharmaceutical carriers, aqueous, powder oroily bases, thickeners and the like may be necessary or desirable.

This invention also includes pharmaceutical compositions which contain,as the active ingredient, the compound of the invention or apharmaceutically acceptable salt thereof, in combination with one ormore pharmaceutically acceptable carriers (excipients). In someembodiments, the composition is suitable for topical administration. Inmaking the compositions of the invention, the active ingredient istypically mixed with an excipient, diluted by an excipient or enclosedwithin such a carrier in the form of, e.g., a capsule, sachet, paper, orother container. When the excipient serves as a diluent, it can be asolid, semi-solid, or liquid material, which acts as a vehicle, carrieror medium for the active ingredient. Thus, the compositions can be inthe form of tablets, pills, powders, lozenges, sachets, cachets,elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solidor in a liquid medium), ointments containing, e.g., up to 10% by weightof the active compound, soft and hard gelatin capsules, suppositories,sterile injectable solutions and sterile packaged powders.

In preparing a formulation, the active compound can be milled to providethe appropriate particle size prior to combining with the otheringredients. If the active compound is substantially insoluble, it canbe milled to a particle size of less than 200 mesh. If the activecompound is substantially water soluble, the particle size can beadjusted by milling to provide a substantially uniform distribution inthe formulation, e.g., about 40 mesh.

The compounds of the invention may be milled using known millingprocedures such as wet milling to obtain a particle size appropriate fortablet formation and for other formulation types. Finely divided(nanoparticulate) preparations of the compounds of the invention can beprepared by processes known in the art see, e.g., WO 2002/000196.

Some examples of suitable excipients include lactose, dextrose, sucrose,sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates,tragacanth, gelatin, calcium silicate, microcrystalline cellulose,polyvinylpyrrolidone, cellulose, water, syrup and methyl cellulose. Theformulations can additionally include: lubricating agents such as talc,magnesium stearate and mineral oil; wetting agents; emulsifying andsuspending agents; preserving agents such as methyl- andpropylhydroxy-benzoates; sweetening agents; and flavoring agents. Thecompositions of the invention can be formulated so as to provide quick,sustained or delayed release of the active ingredient afteradministration to the patient by employing procedures known in the art.

In some embodiments, the pharmaceutical composition comprises silicifiedmicrocrystalline cellulose (SMCC) and at least one compound describedherein, or a pharmaceutically acceptable salt thereof. In someembodiments, the silicified microcrystalline cellulose comprises about98% microcrystalline cellulose and about 2% silicon dioxide w/w.

In some embodiments, the composition is a sustained release compositioncomprising at least one compound described herein, or a pharmaceuticallyacceptable salt thereof, and at least one pharmaceutically acceptablecarrier. In some embodiments, the composition comprises at least onecompound described herein, or a pharmaceutically acceptable saltthereof, and at least one component selected from microcrystallinecellulose, lactose monohydrate, hydroxypropyl methylcellulose andpolyethylene oxide. In some embodiments, the composition comprises atleast one compound described herein, or a pharmaceutically acceptablesalt thereof, and microcrystalline cellulose, lactose monohydrate andhydroxypropyl methylcellulose. In some embodiments, the compositioncomprises at least one compound described herein, or a pharmaceuticallyacceptable salt thereof, and microcrystalline cellulose, lactosemonohydrate and polyethylene oxide. In some embodiments, the compositionfurther comprises magnesium stearate or silicon dioxide. In someembodiments, the microcrystalline cellulose is Avicel PH102™. In someembodiments, the lactose monohydrate is Fast-flo 316™. In someembodiments, the hydroxypropyl methylcellulose is hydroxypropylmethylcellulose 2208 K4M (e.g., Methocel K4 M Premier™) and/orhydroxypropyl methylcellulose 2208 K100LV (e.g., Methocel KOOLV™). Insome embodiments, the polyethylene oxide is polyethylene oxide WSR 1105(e.g., Polyox WSR 1105™).

In some embodiments, a wet granulation process is used to produce thecomposition. In some embodiments, a dry granulation process is used toproduce the composition.

The compositions can be formulated in a unit dosage form, each dosagecontaining from about 5 to about 1,000 mg (1 g), more usually about 100mg to about 500 mg, of the active ingredient. In some embodiments, eachdosage contains about 10 mg of the active ingredient. In someembodiments, each dosage contains about 50 mg of the active ingredient.In some embodiments, each dosage contains about 25 mg of the activeingredient. The term “unit dosage forms” refers to physically discreteunits suitable as unitary dosages for human subjects and other mammals,each unit containing a predetermined quantity of active materialcalculated to produce the desired therapeutic effect, in associationwith a suitable pharmaceutical excipient.

The components used to formulate the pharmaceutical compositions are ofhigh purity and are substantially free of potentially harmfulcontaminants (e.g., at least National Food grade, generally at leastanalytical grade, and more typically at least pharmaceutical grade).Particularly for human consumption, the composition is preferablymanufactured or formulated under Good Manufacturing Practice standardsas defined in the applicable regulations of the U.S. Food and DrugAdministration. For example, suitable formulations may be sterile and/orsubstantially isotonic and/or in full compliance with all GoodManufacturing Practice regulations of the U.S. Food and DrugAdministration.

The active compound may be effective over a wide dosage range and isgenerally administered in a therapeutically effective amount. It will beunderstood, however, that the amount of the compound actuallyadministered will usually be determined by a physician, according to therelevant circumstances, including the condition to be treated, thechosen route of administration, the actual compound administered, theage, weight, and response of the individual patient, the severity of thepatient's symptoms and the like.

The therapeutic dosage of a compound of the present invention can varyaccording to, e.g., the particular use for which the treatment is made,the manner of administration of the compound, the health and conditionof the patient, and the judgment of the prescribing physician. Theproportion or concentration of a compound of the invention in apharmaceutical composition can vary depending upon a number of factorsincluding dosage, chemical characteristics (e.g., hydrophobicity), andthe route of administration. For example, the compounds of the inventioncan be provided in an aqueous physiological buffer solution containingabout 0.1 to about 10% w/v of the compound for parenteraladministration. Some typical dose ranges are from about 1 μg/kg to about1 g/kg of body weight per day. In some embodiments, the dose range isfrom about 0.01 mg/kg to about 100 mg/kg of body weight per day. Thedosage is likely to depend on such variables as the type and extent ofprogression of the disease or disorder, the overall health status of theparticular patient, the relative biological efficacy of the compoundselected, formulation of the excipient, and its route of administration.Effective doses can be extrapolated from dose-response curves derivedfrom in vitro or animal model test systems.

For preparing solid compositions such as tablets, the principal activeingredient is mixed with a pharmaceutical excipient to form a solidpreformulation composition containing a homogeneous mixture of acompound of the present invention. When referring to thesepreformulation compositions as homogeneous, the active ingredient istypically dispersed evenly throughout the composition so that thecomposition can be readily subdivided into equally effective unit dosageforms such as tablets, pills and capsules. This solid preformulation isthen subdivided into unit dosage forms of the type described abovecontaining from, e.g., about 0.1 to about 1000 mg of the activeingredient of the present invention.

The tablets or pills of the present invention can be coated or otherwisecompounded to provide a dosage form affording the advantage of prolongedaction. For example, the tablet or pill can comprise an inner dosage andan outer dosage component, the latter being in the form of an envelopeover the former. The two components can be separated by an enteric layerwhich serves to resist disintegration in the stomach and permit theinner component to pass intact into the duodenum or to be delayed inrelease. A variety of materials can be used for such enteric layers orcoatings, such materials including a number of polymeric acids andmixtures of polymeric acids with such materials as shellac, cetylalcohol and cellulose acetate.

The liquid forms in which the compounds and compositions of the presentinvention can be incorporated for administration orally or by injectioninclude aqueous solutions, suitably flavored syrups, aqueous or oilsuspensions, and flavored emulsions with edible oils such as cottonseedoil, sesame oil, coconut oil, or peanut oil, as well as elixirs andsimilar pharmaceutical vehicles.

Compositions for inhalation or insufflation include solutions andsuspensions in pharmaceutically acceptable, aqueous or organic solvents,or mixtures thereof, and powders. The liquid or solid compositions maycontain suitable pharmaceutically acceptable excipients as describedsupra. In some embodiments, the compositions are administered by theoral or nasal respiratory route for local or systemic effect.Compositions can be nebulized by use of inert gases. Nebulized solutionsmay be breathed directly from the nebulizing device or the nebulizingdevice can be attached to a face mask, tent, or intermittent positivepressure breathing machine. Solution, suspension, or powder compositionscan be administered orally or nasally from devices which deliver theformulation in an appropriate manner.

Topical formulations can contain one or more conventional carriers. Insome embodiments, ointments can contain water and one or morehydrophobic carriers selected from, e.g., liquid paraffin,polyoxyethylene alkyl ether, propylene glycol, white Vaseline, and thelike. Carrier compositions of creams can be based on water incombination with glycerol and one or more other components, e.g.,glycerinemonostearate, PEG-glycerinemonostearate and cetylstearylalcohol. Gels can be formulated using isopropyl alcohol and water,suitably in combination with other components such as, e.g., glycerol,hydroxyethyl cellulose, and the like. In some embodiments, topicalformulations contain at least about 0.1, at least about 0.25, at leastabout 0.5, at least about 1, at least about 2 or at least about 5 wt %of the compound of the invention. The topical formulations can besuitably packaged in tubes of, e.g., 100 g which are optionallyassociated with instructions for the treatment of the select indication,e.g., psoriasis or other skin condition.

The amount of compound or composition administered to a patient willvary depending upon what is being administered, the purpose of theadministration, such as prophylaxis or therapy, the state of thepatient, the manner of administration and the like. In therapeuticapplications, compositions can be administered to a patient alreadysuffering from a disease in an amount sufficient to cure or at leastpartially arrest the symptoms of the disease and its complications.Effective doses will depend on the disease condition being treated aswell as by the judgment of the attending clinician depending uponfactors such as the severity of the disease, the age, weight and generalcondition of the patient and the like.

The compositions administered to a patient can be in the form ofpharmaceutical compositions described above. These compositions can besterilized by conventional sterilization techniques, or may be sterilefiltered. Aqueous solutions can be packaged for use as is, orlyophilized, the lyophilized preparation being combined with a sterileaqueous carrier prior to administration. The pH of the compoundpreparations typically will be between 3 and 11, more preferably from 5to 9 and most preferably from 7 to 8. It will be understood that use ofcertain of the foregoing excipients, carriers or stabilizers will resultin the formation of pharmaceutical salts.

The therapeutic dosage of a compound of the present invention can varyaccording to, e.g., the particular use for which the treatment is made,the manner of administration of the compound, the health and conditionof the patient, and the judgment of the prescribing physician. Theproportion or concentration of a compound of the invention in apharmaceutical composition can vary depending upon a number of factorsincluding dosage, chemical characteristics (e.g., hydrophobicity), andthe route of administration. For example, the compounds of the inventioncan be provided in an aqueous physiological buffer solution containingabout 0.1 to about 10% w/v of the compound for parenteraladministration. Some typical dose ranges are from about 1 μg/kg to about1 g/kg of body weight per day. In some embodiments, the dose range isfrom about 0.01 mg/kg to about 100 mg/kg of body weight per day. Thedosage is likely to depend on such variables as the type and extent ofprogression of the disease or disorder, the overall health status of theparticular patient, the relative biological efficacy of the compoundselected, formulation of the excipient, and its route of administration.Effective doses can be extrapolated from dose-response curves derivedfrom in vitro or animal model test systems.

IV. Labeled Compounds and Assay Methods

The compounds of the invention can further be useful in investigationsof biological processes in normal and abnormal tissues. Thus, anotheraspect of the present invention relates to labeled compounds of theinvention (radio-labeled, fluorescent-labeled, etc.) that would beuseful not only in imaging techniques but also in assays, both in vitroand in vivo, for localizing and quantitating TEAD transcription factorin tissue samples, including human, and for identifying TEADtranscription factor ligands by inhibition binding of a labeledcompound. Accordingly, the present invention includes assays thatcontain such labeled compounds.

The present invention further includes isotopically-labeled compounds ofthe invention. An “isotopically” or “radio-labeled” compound is acompound of the invention where one or more atoms are replaced orsubstituted by an atom having an atomic mass or mass number differentfrom the atomic mass or mass number typically found in nature (i.e.,naturally occurring). Suitable radionuclides that may be incorporated incompounds of the present invention include but are not limited to ³H(also written as T for tritium), ¹¹C, ¹³C, ¹⁴C, ¹³N, ¹⁵N, ¹⁵O, ¹⁷O, ¹⁸O,¹⁸F, ³⁵S, ³⁶Cl, ⁸²Br, ⁷⁵Br, ⁷⁶Br, ⁷⁷Br, ¹²³I, ¹²⁴I, ¹²⁵I and ¹³¹I. Theradionuclide that is incorporated in the instant radio-labeled compoundswill depend on the specific application of that radio-labeled compound.For example, for in vitro labeling and competition assays, compoundsthat incorporate ³H, ¹⁴C, ⁸²Br, ¹²⁵I, ¹³¹I, ³⁵S or will generally bemost useful. For radio-imaging applications ¹¹C, ¹⁸F, ¹²⁵I, ¹²³I, ¹²⁴I,¹³¹I, ⁷⁵Br, ⁷⁶Br or ⁷⁷Br will generally be most useful.

It is to be understood that a “radio-labeled” or “labeled compound” is acompound that has incorporated at least one radionuclide. In someembodiments the radionuclide is selected from the group consisting of³H, ¹⁴C, ¹²⁵I, ³⁵S and ⁸²Br. In some embodiments, the compoundincorporates 1, 2 or 3 deuterium atoms. Synthetic methods forincorporating radio-isotopes into organic compounds are known in theart.

Specifically, a labeled compound of the invention can be used in ascreening assay to identify and/or evaluate compounds. For example, anewly synthesized or identified compound (i.e., test compound) which islabeled can be evaluated for its ability to bind a TEAD transcriptionfactor by monitoring its concentration variation when contacting withthe TEAD transcription factor, through tracking of the labeling. Forexample, a test compound (labeled) can be evaluated for its ability toreduce binding of another compound which is known to bind to a TEADtranscription factor (i.e., standard compound). Accordingly, the abilityof a test compound to compete with the standard compound for binding tothe TEAD transcription factor directly correlates to its bindingaffinity. Conversely, in some other screening assays, the standardcompound is labeled and test compounds are unlabeled. Accordingly, theconcentration of the labeled standard compound is monitored in order toevaluate the competition between the standard compound and the testcompound, and the relative binding affinity of the test compound is thusascertained.

V. Kits

The present disclosure also includes pharmaceutical kits useful, e.g.,in the treatment or prevention of TEAD transcription factor-associateddiseases or disorders, such as cancer, which include one or morecontainers containing a pharmaceutical composition comprising atherapeutically effective amount of a compound of Formula (I), or any ofthe embodiments thereof. Such kits can further include one or more ofvarious conventional pharmaceutical kit components, such as, e.g.,containers with one or more pharmaceutically acceptable carriers,additional containers, etc., as will be readily apparent to thoseskilled in the art. Instructions, either as inserts or as labels,indicating quantities of the components to be administered, guidelinesfor administration, and/or guidelines for mixing the components, canalso be included in the kit.

The invention will be described in greater detail by way of specificexamples. The following examples are offered for illustrative purposes,and are not intended to limit the invention in any manner. Those ofskill in the art will readily recognize a variety of non-criticalparameters which can be changed or modified to yield essentially thesame results.

EXAMPLES Compound Synthesis

Experimental:

The MS (Mass Spectral) data provided in the examples were obtained usingthe following equipment: API 2000 LC/MS/MS/Triple quad; Agilent (1260infinity) LCMS-SQD 6120/Single quad and Shimadzu LCMS-2020/Single quad.

The NMR data provided in the examples were obtained using theequipment-¹HNMR: ¹HNMR: Varian −400 MHz, JEOL −400 MHz.

The abbreviations used in the entire specification may be summarizedherein below with their particular meaning.

° C. (degree Celsius); δ (delta); % (percentage); (BOC)₂O (Bocanhydride); bs (Broad singlet); CDCl₃ (Deuterated chloroform); DCM(Dichloromethane); DMF (Dimethyl formamide); DIPEA (N, N-Diisopropylethylamine); DMAP (Dimethyl aminopyridine); (DMSO-d6 (Deuterated DMSO);d (Doublet); dd (Doublet of doublet); Fe (Iron powder); g or gm (gram);HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate); H or H₂ (Hydrogen); H₂O (Water); HCl(Hydrochloric acid); h or hr (Hours); Hz (Hertz); HPLC (High-performanceliquid chromatography); J (Coupling constant); LiOH (Lithium hydroxide);MeOH (Methanol); mmol (Millimol); M (Molar); mL (Millilitre); mg(Milligram); m (Multiplet); mm (Millimeter); MHz (Megahertz); min(Minutes); NaH (Sodium hydride); NaHCO₃ (Sodium bicarbonate); Na₂SO₄(Sodium sulphate); N₂ (Nitrogen); NMR (Nuclear magnetic resonancespectroscopy); Pd/C (palladium carbon); RT (Room Temperature); s(Singlet); TEA (Triethylamine); TFA (Trifluoroacetic acid); TLC (ThinLayer Chromatography); THE (Tetrahydrofuran); t (Triplet); rac.BINAP((±)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene); Pd₂dba₃(Tris(dibenzylideneacetone) dipalladium(0)); XPhos(2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl); in vacuo (undervacuum); eq. (equivalents); ppt (precipitate); NA (not available).

A general procedure for the synthesis of certain exemplified compoundsis shown in Scheme II below:

To a solution of iodide (1 mmol) and amine (1 mmol) in1,2-dichlorobenzene was added potassium carbonate (1.5 mmol) undernitrogen atmosphere followed by copper iodide (0.05 mmol). Resultingmixture was stirred at r.t. for 1 h and then heated at 180° C. for 2days. After completion of the reaction resulting mixture was dilutedwith dichloromethane (50 mL) and filtered through bed of diatomaceousearth. The organic solution was dried with MgSO₄, concentrated in vacuoand purified by flash column chromatography with hexane/ethyl acetate(gradient of pure hexane to 20/1 hexane/ethyl acetate) as eluent Yield40-69%.

Compound 2a was confirmed with proton NMR and Mass spectroscopy (ESI)and (R_(f) of 0.3 with pure hexane as eluent TLC).

For Compound 2a ¹H NMR (500 MHz, CDCl₃): δ 9.46 (s, 1H), 7.98-7.94 (m,1H), 7.40 (s, 1H), 7.35 (m, 1H), 7.28 (d, 1H), 7.19-7.13 (m, 3H), 6.79(m, 1H), 3.90 (s, 3H) ppm. Mass (M+H, 307.1) Yield 56%.

Compound 2b (M+H 306.1), 2c (M+H 375.1), 2d (M+H 325.1), 2e (M+H 443.1)were confirmed with Mass spectroscopy (LC-MS/ESI) and also consistent onTLC with retention factor (R_(f) of 0.3 with pure hexane as eluent).

A general procedure for synthesis of starting material for compoundsCP-59 and CP-65 is shown in Scheme 3 below:

The requisite amine (1 mmol) and chloro-nicotinate (1 mmol) weredissolved in ethylene glycol and then heated at 140° C. for 24 h. Aftercompletion of the reaction resulting mixture was diluted with ethylacetate (50 mL) and washed three times with 20 mL of water. The organicsolution was dried with MgSO₄, concentrated in vacuo and purified byflash column chromatography with hexane/ethyl acetate (gradient of purehexane to 15/1 hexane/ethyl acetate) as eluent. Yield 55-59%

Compound 2f (M+H, 376.1) and 2g (M+H, 322.1) were confirmed withspectroscopy (ESI) and (R_(f) of 0.1 with pure hexane as eluent TLC)

A cross-coupling procedure used in the preparation of several examplecompounds is shown in Scheme 4 below.

To an oven-dried Schlenk tube was added amine (1 mmol) and bromide (1mmol) and toluene (3 mL). To the above homogeneous solution t-BuONa (1.5mmol) was added. After stirring for 5 minutes, Pd₂(dba)₃ (0.05 mmol) andBu₃P (0.075 mmol), were added under nitrogen atmosphere. The mixture wasstirred for 24 h at 110° C. After cooling to r.t., the reaction mixturewas diluted with ethyl acetate (50 mL) and filtered through bed ofdiatomaceous earth. The organic solution was dried with MgSO₄,concentrated in vacuo and purified by flash column chromatography withhexane/ethyl acetate (gradient of pure hexane to 10/1 hexane/ethylacetate) as eluent to give desired product. Yield 42-55%

For Compound 3a ¹H NMR (500 MHz, CDCl₃): δ 9.45 (s, 1H), 8.01 (s, 1H),7.5-7.7.30 (m, 2H), 7.2-7.1 (m, 2H), 6.98 (s, 1H), 6.8 (s, 1H) 6.78-6.26(m, 4H), 5.99 (s, 1H) 3.90 (s, 3H), 2.23-1.97 (m, 15H) ppm

For Compound 3c ¹H NMR (500 MHz, CDCl₃): δ 9.45 (s, 1H), 8.01 (s, 1H),7.45-7.23. (d, 2H), 7.23-7.01 (m, 6H), 6.98-7.01 (d, 2H), 6.94 (s, 1H),3.93 (s, 3H), 5.99 (s, 1H) 2.21-1.98 (m, 15H) ppm

For Compound 3d ¹H NMR (500 MHz, CDCl₃): δ 9.45 (s, 1H), 8.01 (s, 1H),7.45-7.01 (m, 4H), 6.94 (s, 1H), 6.63 (s, 1H) 6.65-6.20 (m, 4H), 5.98(s, 1H) 3.92 (s, 3H), 2.21-1.98 (m, 15H) ppm

A cross-coupling procedure used in the preparation of several examplecompounds is shown in Scheme 5 below.

To an oven-dried Schlenk tube was added amine (1 mmol) and bromide (1mmol) and toluene (3 mL). To the above homogeneous solution t-BuONa (1.5mmol) was added. After stirring for 5 minutes, Pd₂(dba)₃ (0.05 mmol) andBu₃P (0.075 mmol), were added under nitrogen atmosphere. The mixture wasstirred for 24 h at 110° C. After cooling to r.t., the reaction mixturewas diluted with ethyl acetate (50 mL) and filtered through bed ofdiatomaceous earth. The organic solution was dried with MgSO₄,concentrated in vacuo and purified by flash column chromatography withhexane/ethyl acetate (gradient of pure hexane to 10/1 hexane/ethylacetate) as eluent to give desired product. Yield 50-54%

For Compound 3f ¹H NMR (500 MHz, CDCl₃): δ 9.45 (s, 1H), 8.01 (s, 1H),7.49-7.33. (d, 2H), 7.23-7.01 (m, 5H), 6.91-7.04 (d, 2H), 6.94 (s, 1H),3.93 (s, 3H), 5.99 (s, 1H) 2.21-1.98 (m, 15H) ppm

Compound 3g confirmed with LC-MS/ESI (M+H 468.57)

A cross-coupling procedure used in the preparation of several examplecompounds is shown in Scheme 6 below.

To an oven-dried Schlenk tube was added amine (1 mmol) and bromide (1mmol) and toluene (3 mL). To the above homogeneous solution t-BuONa (1.5mmol) was added. After stirring for 5 minutes, Pd₂(dba)₃ (0.05 mmol) andBu₃P (0.075 mmol), were added under nitrogen atmosphere. The mixture wasstirred for 24 h at 110° C. After cooling to r.t., the reaction mixturewas diluted with ethyl acetate (50 mL) and filtered through bed ofdiatomaceous earth. The organic solution was dried with MgSO₄,concentrated in vacuo and purified by flash column chromatography withhexane/ethyl acetate (gradient of pure hexane to 10/1 hexane/ethylacetate) as eluent to give desired product (39-55% yield).

For Compound 3b ¹H NMR (500 MHz, CDCl₃): δ 9.45 (s, 1H), 8.01 (s, 1H),7.67-7.56 (d, 2H), 7.2-7.1 (m, 2H), 6.98 (s, 1H), 6.82 (s, 1H) 6.78-6.26(m, 2H), 5.99 (s, 1H) 3.92 (s, 3H), 2.23-1.97 (m, 15H) ppm

For Compound 3e ¹H NMR (500 MHz, CDCl₃): δ 9.46 (s, 1H), 8.05 (s, 1H),7.79-7.56 (m, 4H), 7.2-6.99 (m, 4H), 6.98 (s, 1H, 5.99 (s, 1H) 3.94 (s,3H), 2.23-1.97 (m, 15H) ppm

Carboxylic acid compounds were prepared by hydrolysis reactions as shownin Schemes 7, 8, 9 and 10, and the experimental procedures describedbelow.

To a solution of ester (1 mmol) in ethanol (10 mL) was added 2 mmol of2N NaOH solution and heated at 40° C. for 24-48 h. Upon completion ofthe reaction, reaction was cooled on ice and acidified with 2NHydrochloride solution and extracted three times with 10 mL of ethylacetate. The organic solution was dried with MgSO₄, concentrated invacuo and purified by flash column chromatography with hexane/ethylacetate (gradient of pure hexane to 5/1 hexane/ethyl acetate) as eluentto give desired product. Yield 70-79%

CP-52 was confirmed by LC-MS (ESI, M+H 439.1).

CP-57 was confirmed by LC-MS (ESI M+H 521.1).

CP-62 was confirmed by LC-MS (ESI M+H 457.1).

To a solution of ester (1 mmol) in ethanol (10 mL) was added 2 mmol of2N NaOH solution and heated at 40° C. for 24-48 h. Upon completion ofthe reaction, reaction was cooled on ice and acidified with 2NHydrochloride solution and extracted three times with 10 mL of ethylacetate. The organic solution was dried with MgSO₄, concentrated invacuo and purified by flash column chromatography with hexane/ethylacetate (gradient of pure hexane to 5/1 hexane/ethyl acetate) as eluentto give desired product. Yield 80-83%

CP-59 was confirmed by LC-MS (ESI, M+H 509.1).

CP-65 was confirmed by LC-MS (ESI, M+H 454.1).

CP-55 was confirmed by LC-MS (ESI, M+H 439.12).

CP-64 was confirmed by LC-MS (ESI, M+H 474.1).

To a solution of ester (1 mmol) in ethanol (10 mL) was added 2 mmol of2N NaOH solution and heated at 40° C. for 24-48 h. Upon completion ofthe reaction, reaction was cooled on ice and acidified with 2NHydrochloride solution and extracted three times with 10 mL of ethylacetate. The organic solution was dried with MgSO₄, concentrated invacuo and purified by flash column chromatography with hexane/ethylacetate (gradient of pure hexane to 5/1 hexane/ethyl acetate) as eluentto give desired product. Yield 73-87%

CP-55 was confirmed by LC-MS (ESI, M+H 521.1).

CP-64 was confirmed by LC-MS (ESI, M+H 575.1).

Carboxylic acid compounds were converted to vinyl ketone compounds asshown in Scheme 11, and the experimental procedures described below.

The acid was converted to Weinreb amide. To a solution of acid (0.1mmol) in dichloromethane (1 mL) was added triethylamine (0.25 mmol)followed by Weinreb amine salt (0.2 mmol), HATU (0.2 mmol) and stirredat r.t. for 16 h. After completion of the reaction, water was and addedand extracted three times with 10 mL of ethyl acetate. The organicsolution was dried with MgSO₄, concentrated in vacuo and purified byflash column chromatography with hexane/ethyl acetate (gradient of purehexane to 5/1 hexane/ethyl acetate) as eluent to give desired product.

An ice cooled solution of Weinreb amide (1 mmol) in anhydrous THF (10mL) was added 4 mL of 1M solution of vinyl magnesium bromide in THF andwarmed to r.t. and stirred for 4 h after completion of the reaction,quenched with 1N hydrochloride solution at 0° C. and extracted threetimes with 10 mL of ethyl acetate. The organic solution was dried withMgSO₄, concentrated in vacuo and purified by flash column chromatographywith hexane/ethyl acetate (gradient of pure hexane to 5/1 hexane/ethylacetate) as eluent to give desired product. Yield 42-57%.

CP-55 was confirmed by LC-MS (ESI, M+H 449.14).

CP-64 was confirmed by LC-MS (ESI, M+H 449.16).

Certain exemplified compound can be synthesized and characterized asdiscussed below.

Intermediate-I

Step-a: Synthesis of N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl) acetamide(Ia)

To a solution of acetanilide (50 g, 369 mmol, 1.0 eq.) in1,1,2,2-tetrachloroethane (300 mL) was added 1-bromoadamantane (87.5 g,406 mmol, 1.1 eq.) and stirred for 5 minutes. Zinc chloride anhydrous(25.1 g, 184 mmol, 0.5 eq.) was added and stirred at 100° C. for 36 h.Reaction mixture was cooled to RT and excess tetrachloroethane wasremoved by concentrating in vacuo. The residue was dissolved in ethylacetate, washed with water and brine. The organic layer was dried overanhydrous Sodium sulfate, adsorbed over silica and purified by flashcolumn chromatography to afford title product as a white solid (58 g,58%).

¹H NMR (400 MHz, DMSO-d6) δ 9.81 (s, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.25(d, J=8.8 Hz, 2H), 2.04 (bs, 2H), 2.00 (s, 3H), 1.82 (s, 6H), 1.72 (s,6H); LC-MS: m/z 270.1 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-Ia using appropriate reactants and reagents in presence ofsuitable solvents and appropriate reaction conditions.

Intermediate CP No. Structure Analytical data 396 Ia.1

¹H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.24(d, J = 8.8 Hz, 2H), 2.13-2.11 (m, 1H), 2.00 (s, 3H), 1.65 (s, 2H),1.49-1.32 (m, 8H), 1.17 (s, 2H), 0.84 (s, 6H). LC-MS: m/z 298.2 (M + H)⁺

Step-b: Synthesis ofN-(4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)acetamide (Ib)

A solution of N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl)acetamide (25 g,92.8 mmol, 1.0 eq.) in DMF (500 mL) at 0° C. was added withN-chlorosuccinimide (13.6 g, 101 mmol, 1.1 eq.). The reaction mixturewas allowed to RT and stirred for 16 h. Excess DMF was removed byconcentrating in vacuo. The residue was dissolved in ethyl acetate,washed with water and brine. The organic layer was dried over anhydrousSodium sulfate and concentrated in vacuo. The crude solid (22 g, 780%)obtained was used in next step without further purification.

¹H NM/R (400 MHz, DMSO-d6) δ 9.42 (s, 1H), 7.58 (d, J=8.3 Hz, 1H), 7.37(d, J=2.5 Hz, 1H), 7.29 (dd, J₁=2.85 Hz, J₂=8.8 Hz, 1H), 2.06 (bs, 6H),1.75 (s, 6H), 1.69 (s, 6H); LC-MS: m/z 304.10 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-Ib using appropriate reactants and reagents in presence ofsuitable solvents and appropriate reaction conditions.

Intermediate CP No. Structure Analytical data 170 Ib.1

¹H NMR (400 MHz, DMSO-d6) δ 8.21-8.19 (m, 1H), 7.53-7.48 (m, 2H),7.31-7.29 (m, 1H), 2.22 (s, 3H), 2.09 (s, 3H), 1.86 (s, 6H), 1.80-1.60(m, 6H). LC-MS: m/z 348.0 M + H)⁺ 396 Ib.2

¹H NMR (400 MHz, DMSO-d6) δ 9.42 (s, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.37(d, J = 1.6 Hz, 1H), 7.28 (dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz, 1H), 2.14-2.12(m, 1H), 2.06 (s, 3H), 1.67 (s, 2H), 1.51-1.32 (m, 8H), 1.18 (s, 2H),0.85 (s, 6H). LC-MS: m/z 332.2 (M + H)⁺

Step-c: Synthesis of 4-((3r,5r,7r)-adamantan-1-yl)-2-chloroaniline(Intermediate-1)

To a solution ofN-(4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)acetamide (17 g, 56mmol, 1.0 eq.) in methanol (150 mL), conc. HCl (150 mL) was added andrefluxed at 100° C. for 8 h. Excess methanol was removed in vacuo. Thewhite ppt. obtained was filtered off. The filtered solid was washed witha solution of Sodium bicarbonate followed by water and dried undervacuum. Desired product was obtained as a white solid (13 g, 880).

¹H NMR (400 MHz, DMSO-d6) δ 7.08 (d, J₁=2.4 Hz, 1H), 7.02 (dd, J₁=1.9Hz, J₂=8.3 Hz, 1H), 6.73 (d, J=8.3 Hz, 1H), 5.09 (bs, 2H), 2.01 (s, 3H),1.76 (s, 6H), 1.66 (s, 6H); LC-MS: m/z 262.2 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-I using appropriate reactants and reagents in presence ofsuitable solvents and appropriate reaction conditions.

Intermediate CP No. Structure Analytical data I.1

¹H NMR (400 MHz, DMSO-d6) δ 6.99 (d, J = 8.3 Hz, 2H), 6.50 (d, J = 8.3Hz, 1H), 4.76 (s, 2H), 2.01 (bs, 3H), 1.77 (s, 6H), 1.70 (s, 6H). LC-MS:m/z 228.1 (M + H)⁺ 295 I.2

¹H NMR (400 MHz, DMSO-d6) δ 7.06 (d, J = 8.4 Hz, 2H), 6.63 (d, J = 7.6Hz, 2H), 6.10-6.00 (bs, 2H), 2.10 (s, 1H), 1.61 (s, 2H), 1.45-1.30 (m,8H), 1.15 (s, 2H), 0.84 (s, 6H). LC-MS: m/z 256.2 (M + H)⁺ 396 I.3

¹H NMR (400 MHz, DMSO-d6) δ 7.19 (d, J = 2.0 Hz, 1H), 7.11 (dd, J₁ = 2.0Hz, J₂ = 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 2.11-2.10 (m, 1H), 1.61(s, 2H), 1.46- 1.30 (m, 8H), 1.15 (s, 2H), 0.84 (s, 6H). LC-MS: m/z290.2 (M + H)⁺ 170 I.4

¹H NMR (400 MHz, DMSO-d6) δ 7.39-7.38 (m, 1H), 7.12-7.09 (m, 1H),6.74-6.72 (m, 1H), 3.94 (s, 2H), 2.09 (s, 3H), 1.86 (s, 6H), 1.80-1.69(m, 6H).

The below intermediates were prepared by a procedure similar to the onesdescribed in literature using appropriate reactants and reagents inpresence of suitable solvents and appropriate reaction conditions.

Intermediate Literature CP No. Structure report Analytical data 113,132, 133 I.5

Journal of the American Chemical Society, 2000, vol. 122, 17, p.4020-4028 ¹H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 3.5 Hz, 1H), 7.19 (t,J = 3.4 Hz, 2H), 7.13 (d, J = 1.9 Hz, 2H), 7.10 (dd, J₁ = 2.0 Hz, J₂ =8.3 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 5.40 (s, 2H), 2.23 (s, 3H).LC-MS: m/z 218.0 (M + H)⁺ 115 I.6

Organic Letters, 2012, vol. 14, 20, p. 5306-5309 ¹H NMR (400 MHz,DMSO-d6) δ 7.73-7.69 (m, 1H), 7.50 (t, J = 7.3 Hz, 1H), 7.49 (t, J = 7.9Hz, 1H), 7.30 (d, J = 5.3 Hz, 1H), 7.22 (d, J = 1.4 Hz, 1H), 7.03 (d, J= 1.0 Hz, 1H), 6.77 (d, J = 8.3 Hz, 1H), 4.11 (s, 2H). LC-MS: m/z 271.9(M + H)⁺ 116 I.7

Journal of Medicinal Chemistry, 2012, vol. 55, 8, p. 3923-3933 ¹H NMR(400 MHz, DMSO-d6) δ 7.46 (dd, J₁ = 3.0 Hz, J₂ = 8.8 Hz, 1H), 7.38-7.34(m, 1H), 7.24-7.22 (m, 1H), 7.07 (d, J = 2.0 Hz, 2H), 6.61 (d, J = 4.4Hz, 2H), 5.25 (s, 2H). LC-MS: m/z 221.9 (M + H)⁺ 118 I.8

Journal of Medicinal Chemistry, 2009, vol. 52, 9, p. 2683-2693 ¹H NMR(400 MHz, DMSO-d6) δ 7.31 (d, J = 1.9 Hz, 1H), 7.28- 7.22 (m, 2H), 7.16(dd, J₁ = 2.5 Hz, J₂ = 8.4 Hz, 1H), 7.05 (d, J = 8.3 Hz, 1H), 6.99-6.95(dt, J₁ = 1.0 Hz, J₂ = 6.3 Hz, 1H), 6.81 (d, J = 8.3 Hz, 1H), 5.38 (s,2H), 3.75 (s, 3H). LC-MS: m/z 233.9 (M + H)⁺ 121 I.9

WO2015/14944, 2015, A1 ¹H NMR (400 MHz, DMSO-d6) δ 7.10-7.05 (m, 3H),6.93 (d, J = 2.0 Hz, 1H), 6.86 (d, J = 8.3 Hz, 1H), 6.77 (dd, J₁ = 1.4Hz, J₂ = 7.8 Hz, 1H), 5.34 (s, 2H), 1.99 (s, 6H). 122 I.10

Journal of Medicinal Chemistry, 2009, vol. 52, 9, p. 2683-2693 ¹H NMR(400 MHz, DMSO-d6) δ 7.51 (d, J = 7.3 Hz, 1H), 7.38- 7.32 (m, 3H), 7.26(d, J = 2.0 Hz, 1H), 7.12 (dd, J₁ = 1.9 Hz, J₂ = 8.3 Hz, 1H), 6.85 (d, J= 8.4 Hz, 1H), 5.53 (s, 2H). LC- MS: m/z 238.1 (M + H)⁺ 126 I.11

Journal of Medicinal Chemistry, 2009, vol. 52, 9, p. 2683-2693 LC-MS:m/z 232.0 (M + H)⁺ 140 I.12

WO2012/137181, 2012, A1 ¹H NMR (400 MHz, DMSO-d6) δ 7.19 (t, J = 2.0 Hz,1H), 7.10 (dd, J1 = 2.0 Hz, J2 = 8.3 Hz, 1H), 6.72 (d, J = 8.3 Hz, 1H),5.78 (s, 1H), 5.28 (s, 2H), 2.33 (m, 2H), 1.82-1.71 (m, 4H), 0.77- 0.74(m, 6H). 146 I.13

Journal of Medicinal Chemistry, 2002, vol. 45, 8, p. 1697-1711 ¹H NMR(400 MHz, DMSO-d6) δ 7.47-7.40 (m, 4H), 7.32 (d, J = 1.6 Hz, 1H), 7.25(d, J = 7.2 Hz, 2H), 7.05 (d, J = 1.2 Hz, 1H), 6.94 (d, J = 8.4 Hz, 2H),6.41 (d, J = 8.8 Hz, 2H). LC-MS: m/z 236.1 (M + H)⁺ 178 I.14

U.S. Pat. No. 5,200,550 A1 ¹H NMR (400 MHz, DMSO-d6) δ 12.91 (bs, 1H),7.93 (t, J = 1.2 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 8.0 Hz,1H), 7.44 (t, J = 8.0 Hz, 1H), 2.07 (s, 3H), 1.88 (s, 6H), 1.75 (s, 6H).177, 191, 200, I.15

Journal of the Chemical Society, Perkin Transactions 2: Physical OrganicChemistry (1972- 1999), 1976, p. 662-668 ¹H NMR (400 MHz, DMSO-d6) δ7.92 (t, J = 7.8 Hz, 1H), 6.56 (t, J = 2.0 Hz, 1H), 6.49 (d, J = 7.9 Hz,1H), 6.35 (dd, J₁ = 0.9 Hz, J₂ = 7.9 Hz, 1H), 4.86 (s, 2H), 2.03 (s,3H), 1.75 (s, 6H), 1.71 (s, 6H). 193 I.16

Chemistry-A European Journal, 2011, vol. 17, 49, p. 13832-13846 ¹H NMR(400 MHz, DMSO-d6) δ 7.34 (d, J = 7.8 Hz, 1H), 7.24 (t, J = 0.9 Hz, 1H),7.14 (t, J = 1.0 Hz, 1H), 7.05 (d, J = 1.0 Hz, 1H), 6.91 (d, J = 9.0 Hz,2H), 6.60 (d, J = 8.3 Hz, 2H), 5.08 (s, 2H), 3.08 (m, 1H), 1.10 (d, J =6.9 Hz, 6H). 287 I.17

Advanced Synthesis and Catalysis, 2007, vol. 349, 10, p. 1775-1780LC-MS: m/z 235.2 (M + H)⁺ 288 I.18

Journal of Medicinal Chemistry, 1997, vol. 40, 16, p. 2634-2642 ¹H NMR(400 MHz, CDCl3) δ 6.65-6.63 (m, 4H), 3.14 (s, 2H), 3.12 (m, 4H), 1.48(m, 4H), 1.32 (m, 4H), 0.91 (m, 6H). 292 I.19

Antibiotics Chemotherapy, 1954, vol. 4, p. 150, 152 ¹H NMR (400 MHz,DMSO-d6) δ 7.05 (t, J = 7.3 Hz, 2H), 6.81 (d, J = 6.8 Hz, 2H), 6.60-6.52 (m, 5H), 5.02 (s, 2H), 3.48 (t, J = 7.8 Hz, 2H), 1.52-1.46 (m, 2H),1.33-1.27 (m, 2H), 0.86 (t, J = 3.9 Hz, 3H). 291, 328 I.20

WO2008/82003, 2008, A1 LC-MS: m/z 181.10 (M + H)⁺ 309 I.21

Organic and Biomolecular Chemistry, 2006, vol. 4, 6, p. 1091- 1096 ¹HNMR (400 MHz, DMSO-d6) δ 7.42-7.35 (m, 4H), 2.05 (s, 3H), 1.84 (s, 6H),1.73 (s, 6H). LC-MS: m/z 237.1 (M + H)⁺ 318 I.22

WO2010/125390, 2010, A1 LC-MS: m/z 284.2 (M- 113)⁺ Azetidine fragment338 I.23

Pharmazie, 1981, vol. 36, 6, p. 400- 402 ¹H NMR (400 MHz, DMSO-d6) δ7.50 (d, J = 8.0 Hz, 2H), 7.02 (s, 1H), 6.49 (d, J = 8.4 Hz, 2H), 5.50(s, 2H), 2.03 (s, 9H), 1.64 (s, 6H). LC-MS: m/z 271.15 (M + H)⁺ 203 I.24

Organic Letters, 2007, vol. 9, 26, p. 5397-5400 ¹H NMR (400 MHz,DMSO-d6) δ 8.07-8.05 (m, 1H), 7.94 (s, 1H), 7.61-7.57 (m, 2H), 7.30 (d,J = 7.2 Hz, 1H), 7.28- 7.24 (m, 1H), 7.20-7.16 (m, 2H), 4.20 (s, 2H),3.11-3.07 (m, 1H), 1.06 (d, J = 6.8 Hz, 6H). 321 I.25

Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176 ¹H NMR (400MHz, DMSO-d6) δ 9.83 (s, 1H), 7.22-7.21 (m, 1H), 7.12-7.10 (m, 1H),6.90- 6.88 (m, 1H), 2.03 (s, 3H), 1.79 (s, 6H), 1.71 (s, 6H). 323 I.26

WO2015/51149, 2015, A1 ¹H NMR (400 MHz, DMSO-d6) δ 6.62 (d, J = 8.8 Hz,2H), 6.48 (d, J = 8.8 Hz, 2H), 4.54 (s, 2H), 3.37 (s, 2H), 1.96 (s, 3H),1.69-1.59 (m, 12H). 337 I.27

Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176 ¹H NMR (400MHz, DMSO-d6) δ 7.17 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H),2.98- 2.96 (m, 4H), 2.92-2.88 (m, 1H), 2.81-2.80 (m, 4H), 2.03 (s, 3H),1.81 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 297.3 (M + H)⁺ 388 I.28

Antibiotics Chemotherapy, 1954, vol. 4, p. 150, 152 ¹H NMR (400 MHz,DMSO-d6) δ 7.12-7.08 (m, 2H), 6.96 (d, J = 2.0 Hz, 1H), 6.86-6.80 (m,2H), 6.64-6.58 (m, 3H), 5.30 (s, 2H), 3.50 (t, J = 7.2 Hz, 2H), 1.51-1.46 (m, 2H), 1.35-1.28 (m, 2H), 0.87 (t, J = 7.2 Hz, 3H). LC-MS: m/z275.1 (M + H)⁺ 407, 408 I.29

Tetrahedron, 1988, vol. 44, 7, p. 1893-1904 ¹H NMR (400 MHz, DMSO-d6) δ7.26-7.24 (m, 4H), 3.66 (s, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s,6H). LC- MS: m/z 242.2 (M + H)⁺ 314 I.30

Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176 ¹H NMR (400MHz, DMSO-d6) δ 9.07 (s, 1H), 7.13-7.11 (m, 2H), 6.68-6.66 (m, 2H), 2.03(s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 228.0 (M + H)⁺ 383 I.31

Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176 ¹H NMR (400MHz, DMSO-d6) δ 6.87-6.83 (m, 1H), 6.65 (dd, J₁ = 2.8 Hz, J₂ = 8.8 Hz,1H), 6.15 (d, J = 8.4 Hz, 1H), 2.08- 2.05 (m, 1H), 1.54 (s, 2H),1.38-1.29 (m, 8H), 1.11 (s, 2H), 0.82 (s, 6H). LC-MS: m/z 289.05 (M −H)⁻. 360 I.32

Chemistry-A European Journal, 2011, vol. 17, 49, p. 13832-13846 ¹H NMR(400 MHz, DMSO-d6) δ 10.20 (s, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.32 (t, J= 7.4 Hz, 1H), 7.19 (t, J = 6.3 Hz, 2H), 7.09 (d, J = 7.3 Hz, 1H), 7.03(t, J = 8.3 Hz, 2H), 2.99-2.96 (m, 1H), 1.11 (d, J = 6.9 Hz, 6H). LC-MS:m/z 245.1 (M − H)⁻. 93 I.33

Chemistry-A European Journal, 2011, vol. 17, 49, p. 13832-13846 LC-MS:m/z 246.0 (M + H)⁺

Intermediate-II

Step-a: Synthesis of methyl 2-((4-bromophenyl)amino)benzoate(Intermediate-II)

A solution of methyl 2-iodobenzoate (30 g, 114.5 mmol, 1.0 eq.) and4-bromoaniline (19.3 g, 114.5 mmol, 1.0 eq.) in toluene (500 mL) wasadded with cesium carbonate (49 g, 150 mmol, 1.3 eq.) and de-gassed withN₂ gas for 15 min. Palladium acetate (1.28 g, 5.7 mmol, 0.05 eq.) andrac. BINAP (3.56 g, 5.7 mmol, 0.05 eq.) were added and de-gassed for 5min. Reaction mass was heated at 110° C. for 16 h. Reaction mass wasfiltered through celite, concentrated in vacuo and purified bycombi-flash to afford the title product as pale brown liquid (33 g,940%).

¹H NMR (400 MHz, DMSO-d6) δ 9.25 (s, 1H), 7.89 (dd, J₁=2.0 Hz, J₂=8.3Hz, 1H), 7.51 (d, J=2.9 Hz, 2H), 7.48 (t, J=1.9 Hz, 1H), 7.26 (d, J=7.8Hz, 1H), 7.21 (d, J=4.9 Hz, 2H), 6.87 (t, J=1.0 Hz, 1H), 3.84 (s, 3H);LC-MS: m/z 307.9 (M+H)²⁺

The below intermediates were prepared by a procedure similar toIntermediate-II using appropriate reactants and reagents employingsuitable Pd & Fe catalysts and ligands and in presence of suitablesolvents and appropriate reaction conditions.

Intermediate CP No. Structure Analytical data  52 II.1

LC-MS: m/z 308 (M + H)²⁺ 127 II.2

¹H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 8.20 (d, J = 5.6 Hz, 1H),7.89-7.82 (m, 2H), 7.64 (t, J = 8.4 Hz, 1H), 7.27 (t, J = 7.6 Hz, 1H),6.84 (d, J = 6.0 Hz, 1H), 3.77 (s, 3H). LC-MS: m/z 263.9 (M + H)⁺ 141154 II.3

¹H NMR (400 MHz, DMSO-d6) δ 10.83 (s, 1H), 8.69 (s, 2H), 8.57 (d, J =8.4 Hz, 1H), 7.98 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H), 7.66-7.61 (m, 1H),7.11 (t, J = 7.6 Hz, 1H), 3.86 (s, 3H). LC-MS: m/z 309.9 (M + H)²⁺ 142252 II.4

¹H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.35 (d, J = 1.6 Hz, 1H),8.29-8.26 (m, 2H), 7.94 (dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H), 7.60 (t, J =8.0 Hz, 1H), 7.11 (t, J = 8.0 Hz, 1H), 3.84 (s, 3H). LC-MS: m/z 309.9(M + H)²⁺ 144, 152, 155 II.5

¹H NMR (400 MHz, DMSO-d6) δ 10.18 (s, 1H), 8.39 (d, J = 8.8 Hz, 1H),8.30 (d, J = 2.4 Hz, 1H), 7.92 (dd, J₁ = 1.2 Hz, J2 = 7.6 Hz, 1H), 7.83(dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 1H), 7.56 (t, J = 7.2 Hz, 1H), 7.04-6.98(m, 2H), 3.84 (s, 3H). LC-MS: m/z 308.9 (M + H)²⁺ 158 II.6

¹H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1H), 7.63 (t, J = 1.5 Hz, 1H),7.44-7.40 (m, 4H), 7.33-7.30 (m, 1H), 7.06-7.02 (m, 2H), 3.83 (s, 3H).LC- MS: m/z 307.9 (M + H)²⁺ 175 II.7

¹H NMR (400 MHz, DMSO-d6) δ 10.72 (s, 1H), 8.52 (dd, J₁ = 2.0 Hz, J₂ =4.8 Hz, 1H), 8.49 (d, J = 9.0 Hz, 1H), 8.39 (d, J =0 2.4 Hz, 1H), 8.34(dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H), 8.0 (dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz,1H), 7.06 (dd, J₁ = 5.2 Hz, J₂ = 8.0 Hz, 1H), 3.91 (s, 3H). LC-MS: m/z310 (M + H)²⁺ 194 II.8

¹H NMR (400 MHz, DMSO-d6) δ 8.29 (dd, J₁ = 1.6 Hz, J₂ = 4.4 Hz, 1H),7.95 (dd, J₁ = 2.0 Hz, J₂ = 7.2 Hz, 1H), 6.86 (dd, J₁ = 5.2 Hz, J₂ = 8.0Hz, 1H), 3.82 (s, 3H), 3.42 (s, 4H), 3.29-3.25 (m, 4H). 200, 233, 241,247 II.9

¹H NMR (400 MHz, DMSO-d6) δ 10.15 (s, 1H), 8.46 (dd, J₁ = 1.4 Hz, J₂ =4.9 Hz, 1H), 8.28 (dd, J₁ = 1.4 Hz, J₂ = 7.8 Hz, 1H), 8.20 (s, 1H), 7.56(d, J = 7.8 Hz, 1H), 7.27 (t, J = 8.3 Hz, 1H), 7.19 (d, J = 7.8 Hz, 1H),6.97- 6.94 (m, 1H), 3.91 (s, 3H). LC-MS: m/z 306.9 (M + H)⁺ 218, 385,386, 389 II.10

¹H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H), 8.44 (dd, J₁ = 1.6 Hz, J₂ =4.8 Hz, 1H), 8.28 (dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H), 7.72 (d, J = 9.2Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 6.95- 6.92 (m, 1H), 3.91 (s, 3H).LC-MS: m/z 307.1 (M + H)⁺ 223 II.11

¹H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.56 (d, J = 1.0 Hz, 2H), 8.01(s, 1H), 7.66-7.60 (m, 1H), 7.34- 7.29 (m, 2H), 7.06-7.03 (m, 1H). LC-MS: m/z 294.0 (M + H)⁺ 242 II.12

¹H NMR (400 MHz, DMSO-d6) δ 9.98 (s, 1H), 8.28-8.26 (m, 2H), 8.06- 8.04(m, 1H), 7.92-7.89 (m, 1H), 7.72-7.68 (m, 1H), 7.28 (t, J = 0.8 Hz, 1H).LC-MS: m/z 295.0 (M + H)⁺ 243 II.13

¹H NMR (400 MHz, DMSO-d6) δ 9.67 (s, 1H), 8.3 (m, 2H), 7.59 (d, J = 8.8Hz, 2H), 7.30 (m, 3H), 7.11 (d, J =8.8 Hz, 2H), 6.72 (d, J = 8.9 Hz,2H), 3.85 (s, 3H). 251 II.14

¹H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H), 8.70 (d, J = 1.0 Hz, 1H),8.38 (d, J = 2.4 Hz, 1H), 8.24 (dd, J₁ = 1.9 Hz, J₂ = 8.8 Hz, 1H), 7.73(dd, J₁ = 2.4 Hz, J₂ = 8.3 Hz, 1H), 7.62-7.56 (m, 1H), 7.01 (t, J = 1.5Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H). LC-MS: m/z 295.9 (M + H)²⁺ 254 II.15

¹H NMR (400 MHz, DMSO-d6) δ 10.38 (s, 1H), 8.49 (dd, J₁ = 1.5 Hz, J₂ =4.4 Hz, 1H), 8.31 (dd, J₁ = 1.9 Hz, J₂ = 7.8 Hz, 1H), 7.89-7.84 (m, 4H),7.02-6.99 (m, 1H), 3.92 (s, 3H), 1.54 (s, 9H). 259, 346 II.16

¹H NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H), 7.97 (d, J = 8.8 Hz, 2H),7.83-7.78 (m, 3H), 7.52 (d, J = 7.3 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H),4.37- 4.32 (m, 2H), 1.54 (s, 9H), 1.36 (t, J = 6.8 Hz, 3H). 264 II.17

¹H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.15 (dd, J₁ = 1.2 Hz, J₂ =5.6 Hz, 1H), 7.69-7.66 (m, 2H), 7.59-7.55 (m, 1H), 7.42-7.39 (m, 2H),6.82 (d, J = 8.0 Hz, 1H), 6.78-6.75 (m, 1H). LC-MS: m/z 249.0 (M + H)⁺265 II.18

¹H NMR (400 MHz, DMSO-d6) δ 9.30 (s, 1H), 8.11 (dd, J₁ = 1.2 Hz, J₂ =8.0 Hz, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.58 (t, J = 6.8 Hz, 1H), 7.47(d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.09-7.05 (m, 1H), 1.54(s, 9H). LC-MS: m/z 313.0 (M − H)⁻ 269 II.19

¹H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.56-8.51 (m, 2H), 7.66- 7.64(m, 2H), 7.54-7.52 (m, 2H), 7.02 (dd J₁ = 5.2 Hz, J₂ = 8.4 Hz, 1H). 274,285, II.20

¹H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.83(d, J = 8.3 Hz, 2H), 7.53-7.44 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 6.98(t, J = 7.8 Hz, 1H), 3.84 (s, 3H), 1.53 (s, 9H). LC-MS: m/z 328.0 (M +H)⁺ 302 II.21

¹H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.41 (dd, J₁ = 2.0 Hz, J₂ =4.9 Hz, 1H), 8.26 (dd, J₁ = 1.9 Hz, J₂ = 7.8 Hz, 1H), 7.66 (d, J = 8.8Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.88 (m, 1H), 3.90 (s, 3H), 3.50 (s,2H), 1.42 (s, 9H). LC-MS: m/z 343.0 (M + H)⁺ 303 II.22

¹H NMR (400 MHz, DMSO-d6) δ 8.93 (s, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.73(s, 1H), 7.55-7.50 (m, 1H), 7.44 (d, J = 4.4 Hz, 2H), 7.09 (d, J = 8.8Hz, 2H), 3.84 (s, 3H), 1.53 (s, 9H). LC-MS: m/z 328.0 (M + H)⁺ 327 II.23

¹H NMR (400 MHz, DMSO-d6) δ 9.48 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.74(t, J = 7.6 Hz, 1H), 7.47-7.42 (m, 3H), 7.05 (d, J = 8.4 Hz, 1H), 4.35-4.30 (m, 2H), 1.35 (t, J = 7.2 Hz, 3H). LC-MS: m/z 321.0 (M + H)⁺ 330II.24

LC-MS: m/z 288.0 (M − 56H)⁺; t-butyl fragment 333, 408 II.25

¹H NMR (400 MHz, DMSO-d6) δ 9.31 (s, 1H), 7.96-7.90 (m, 1H), 7.72 (s,1H), 7.59-7.57 (m, 1H), 7.50-7.44 (m, 3H), 7.25 (d, J = 8.4 Hz, 1H),3.82 (s, 3H), 1.50 (s, 9H). LC-MS: m/z 328.2 (M + H)⁺ 334 II.26

¹H NMR (400 MHz, DMSO-d6) δ 7.91 (d, J = 9.3 Hz, 1H), 7.88 (d, J = 8.8Hz, 2H), 7.69 (t, J = 7.8 Hz, 1H), 7.40 (t, J = 7.8 Hz, 1H), 7.20 (d, J= 8.3 Hz, 1H), 6.93 (d, J = 8.8 Hz, 2H), 3.67 (s, 3H), 1.53 (s, 9H). 347II.27

¹H NMR (400 MHz, DMSO-d6) δ 7.57 (s, 1H), 7.29 (d, J = 8.8 Hz, 2H), 7.21(d, J = 7.6 Hz, 1H), 7.15-7.12 (m, 2H), 6.97-6.94 (m, 1H), 6.77 (d, J =8.8 Hz, 2H), 2.17 (s, 3H). LC-MS: m/z 262.0 (M + H)⁺ 651 II.28

LC-MS: m/z 324.05 (M + H)⁺ 638 II.29

LC-MS: m/z 310.1 (M + H)⁺

Intermediate-II.28

Step-a: Synthesis of methyl2-((5-bromopyrimidin-2-yl)(tert-butoxycarbonyl)amino)benzoate (II.28)

To a solution of Intermediate-II.3 (1.3 g, 4.3 mmol, 1 eq.) in THF (30mL), DMAP (0.1 g, 0.84 mmol, 0.2 eq.), pyridine (0.67 g, 8.7 mmol, 2eq.), Boc anhydride (1.38 g, 6.3 mmol, 1.5 eq.) were added and heated at60° C. overnight. Reaction mass was concentrated in vacuo and purifiedby combi-flash to afford title product as off-white solid (1.4 g, 82%).LC-MS: m/z 408.2 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-II.28 using appropriate reactants and reagents and inpresence of suitable solvents and appropriate reaction conditions.

Intermediate CP No. Reactant Structure Analytical data 142 II.29 II.4

LC-MS: m/z 408.9 (M + H)⁺ 152 II.30 II.5

LC-MS: m/z 409.9 (M + H)²⁺ 175 II.31 II.7

LC-MS: m/z 410.1 (M + H)²⁺

The below intermediates were prepared by a procedure similar toIntermediate-II using appropriate reactants and reagents employingsuitable Pd catalysts and ligands and in presence of suitable solventsand appropriate reaction conditions.

Intermediate CP No. Reactant Structure Analytical data 357 II.32 Int-II

LC-MS: m/z 419.1 (M + H)⁺ 363 II.33 I.1

¹H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 7.6 (s, 1H), 7.33-7.25 (m,5H), 7.04 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H),1.73 (s, 6H). LC-MS: m/z 362.3 (M + H)⁺ 394 II.34

LC-MS: m/z 329.2 (M + H)⁺ 315, 316 II.35 I.1

LC-MS: m/z 362.3 (M + H)⁺

Intermediates-IIIa & IIIb

Step-a: Synthesis of ethyl 2-(5-bromo-1H-indazol-1-yl)acetate & ethyl2-(5-bromo-2H-indazol-2-yl)acetate (IIIa & IIIb)

A solution of 5-bromo-1H-indazole (1 g, 5.1 mmol, 1.0 eq.) inacetonitrile (25 mL) was added with potassium carbonate (1.8 g, 12.8mmol, 2.5 eq.) under stirring. Ethyl bromoacetate (0.7 mL, 6.1 mmol, 1.2eq.) was added drop wise and reaction mass was heated at refluxovernight. Reaction mass was concentrated in vacuo, adsorbed over silicaafter water washings and purified by combi-flash to afford titleproducts IIIa (400 mg, 28%, white solid) and IIIb (180 mg, 13%, yellowsolid).

Intermediate-IIIa: ¹H NMR (400 MHz, DMSO-d6) δ 8.10 (s, 1H), 8.05 (s,1H), 7.68-7.65 (m, 1H), 7.53-7.51 (m, 1H), 5.40 (s, 2H), 4.18-4.12 (m,2H), 1.19 (t, J=6.8 Hz, 3H); LC-MS: m/z 283.0 (M+H)⁺

Intermediate-IIIb: ¹H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 8.02 (s,1H), 7.60-7.58 (m, 1H), 7.35-7.32 (m, 1H), 5.42 (s, 2H), 4.20-4.15 (m,2H), 1.18 (t, J=6.4 Hz, 3H); LC-MS: m/z 283.0 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediates-IIIa & IIIb using appropriate reactants and reagents andin presence of suitable solvents and appropriate reaction conditions.

Intermediate CP No. Structure Analytical data 187 III.1

¹H NMR (400 MHz, DMSO-d6) δ 7.49 (d, J = 7.6 Hz, 2H), 7.25 (d, J = 8.0Hz, 2H), 3.81 (d, J = 13.6 Hz, 1H), 3.58 (s, 3H), 3.49 (d, J = 12.4 Hz,1H), 3.27 (dd, J₁ = 5.2 Hz, J₂ = 8.8 Hz, 1H), 2.85-2.80 (m, 1H),2.38-2.32 (m, 1H), 2.09-2.04 (m, 1H), 1.84-1.71 (m, 3H). 192 III.2

¹H NMR (400 MHz, DMSO-d6) δ 7.62 (s, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.15(s, 1H), 7.11 (d, J = 8.4 Hz, 2H), 5.58 (s, 2H), 4.25- 4.23 (m, 2H),2.50 (t, J = 2.0 Hz, 3H). LC- MS: m/z 308.9 (M + H)⁺ 195 III.3

Proceeded with crude/only TLC reference 197 III.4

¹H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 9.2 Hz, 1H), 7.88 (dd, J₁ = 1.6Hz, J₂ = 10 Hz, 1H), 7.27-7.55 (m, 1H), 7.42-7.34 (m, 1H), 5.26 (d, J =2.8 Hz, 2H), 4.20-4.14 (m, 2H), 1.25-1.20 (m, 3H). LC-MS: m/z 282.9 (M +H)⁺ 201 III.5

¹H NMR (400 MHz, DMSO-d6) δ 8.65 (s, 1H), 7.98 (s, 1H), 7.56 (d, J = 8.4Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 5.4 (s, 2H). LC-MS: m/z 238 (M + H)⁺202 III.6

¹H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.29 (s, 1H), 7.43-7.42 (m,1H), 7.37- 7.35 (m, 1H), 7.22-7.19 (m, 1H), 5.47 (s, 2H), 2.05 (s, 3H),1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 372.1 (M + H)⁺ 210 III.7

¹H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 8.03 (s, 1H), 7.74 (d, J = 8.4Hz, 1H), 7.29 (dd, J₁ = 1.6 Hz, J₂ = 8.4 Hz, 1H), 5.38 (s, 2H), 4.14 (q,J = 14 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H). LC-MS: m/z 285.0 (M + H)²⁺ 213III.8

¹H NMR (400 MHz, DMSO-d6) δ 8.47 (s, 1H), 7.87 (s, 1H), 7.56-7.54 (dd,J₁ = 0.8 Hz, J₂ = 6.4 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 5.35 (s, 2H),4.23-4.18 (m, 2H), 1.26 (t, J = 7.6 Hz, 3H). LC-MS: m/z 309.0 (M + H)⁺214 III.9

LC-MS: m/z 306.0 (M + H)⁺ 217 III.10

¹H NMR (400 MHz, DMSO-d6) δ 7.51-7.49 (dd, J₁ = 2.0 Hz, J₂ = 6.8 Hz,2H), 7.29 (t, J = 2.0 Hz, 1H), 7.0 (d, J = 8.0 Hz, 2H), 6.91- 6.9 (dd,J₁ = 2.0 Hz, J₂ = 4.0 Hz, 1H), 6.20- 6.18 (dd, J₁ = 1.2 Hz, J₂ = 4.0 Hz,1H), 5.51 (s, 2H), 4.16-4.11 (m, 2H), 1.12 (t, J = 6.8 Hz, 3H). LC-MS:m/z 308.0 (M + H)⁺ 219 III.11

¹H NMR (400 MHz, DMSO-d6) δ 7.70 (s, 1H), 7.51 (d, J = 2.0 Hz, 1H), 7.36(s, 1H), 7.18-7.14 (m, 1H), 6.3 (s, 1H), 5.14 (s, 2H), 4.17-4.12 (m,2H), 1.24-1.19 (m, 3H). LC- MS: m/z 282.1 (M + H)⁺ 220 III.12

¹H NMR (400 MHz, DMSO-d6) δ 8.01 (d, J = 0.8 Hz, 1H), 7.92 (s, 1H), 7.58(s, 1H), 7.52 (d, J = 6.0 Hz, 1H), 7.34-7.33 (m, 2H), 5.25 (s, 2H), 3.72(s, 3H). LC-MS: m/z 295.0 (M + H)⁺ 221 III.13

¹H NMR (400 MHz, DMSO-d6) δ 8.19 (s, 1H), 7.71 (d, J = 1.2 Hz, 1H),7.49-7.47 (dd, J₁ = 0.8 Hz, J₂ = 7.6 Hz, 1H), 7.37 (s, 1H), 7.3 (t, J =8.0 Hz, 1H), 7.13 (d, J = 7.6 Hz, 1H), 5.52 (s, 2H), 3.73 (s, 3H).LC-MS: m/z 295.1 (M + H)⁺ 227 III.14

¹H NMR (400 MHz, DMSO-d6) δ 7.74 (d, J = 1.2 Hz, 1H), 7.39-7.37 (m, 2H),7.23 (dd, J₁ = 1.6 Hz, J₂ = 8.8 Hz, 1H), 6.45 (d, J = 3.2 Hz, 1H), 5.13(s, 2H), 4.13 (q, J = 14.4 Hz, 2H), 1.2 (t, J = 7.2 Hz, 3H). LC-MS: m/z282.0 (M + H)⁺ 250 III.15

¹H NMR (400 MHz, DMSO-d6) δ 7.51 (d, J = 8.3 Hz, 2H), 7.24 (d, J = 8.3Hz, 2H), 3.57 (s, 3H), 3.43 (s, 2H), 2.75-2.67 (m, 1H), 2.60-2.51 (m,1H), 2.33-2.32 (m, 1H), 2.17- 2.12 (m, 1H), 2.07-2.05 (m, 1H), 1.79-1.77(m, 1H), 1.67-1.63 (m, 1H), 1.49-1.39 (m, 2H). LC-MS: m/z 314.0 (M +H)²⁺

Intermediate-IV

Step-a: Synthesis of methyl 2-(4-bromobenzamido)benzoate(Intermediate-IV)

A solution of methyl 2-aminobenzoate (5 g, 33.1 mmol, 1.0 eq.) in DCM(50 mL) was added with triethylamine (11 g, 108 mmol, 3 eq.) followed by4-bromobenzoyl chloride (7.2 g, 33.1 mmol, 1.0 eq.) and stirred at RTovernight. Reaction mixture was extracted with ethyl acetate from waterand concentrated in vacuo. The crude was washed with n-pentane and driedto afford title product (9 g, 85%).

¹H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 8.47 (d, J=8.3 Hz, 1H), 8.04(d, J=8.4 Hz, 1H), 7.89 (d, J=8.8 Hz, 2H), 7.83 (d, J=8.8 Hz, 2H), 7.67(t, J=7.3 Hz, 1H), 7.24 (t, J=7.3 Hz, 1H), 3.87 (s, 3H).

The below intermediates were prepared by a procedure similar toIntermediate-IV using appropriate reactants and reagents and in presenceof suitable solvents and appropriate reaction conditions.

Intermediate CP No. Structure Analytical data 178 IV.1

LC-MS: m/z 387.4 (M + H)⁺ 239 IV.2

¹H NMR (400 MHz, DMSO-d6) δ6 13.10 (bs, 1H), 10.63 (s, 1H), 7.58 (d, J =5.4 Hz, 2H), 7.47 (d, J = 6.8 Hz, 2H), 1.44 (s, 4H). LC-MS: m/z 284.0(M + H)⁺ 291 IV.3

LC-MS: m/z 345.0 (M + H)⁺ 317 IV.4

Proceeded with crude/only TLC reference 328 IV.5

LC-MS: m/z 345.0 (M + H)²⁺

Intermediate-V

Step-a: Synthesis of methyl 2-((4-bromophenyl)(methyl)amino)nicotinate(Intermediate-V)

A solution of Intermediate-II.10 (0.4 g, 1.3 mmol, 1.0 eq.) in DMF (3mL) was added with sodium hydride (50% o, 0.16 g, 3.9 mmol, 3 eq.) andstirred for 10 min. Iodomethane (0.25 mL, 3.9 mmol, 3 eq.) was addeddrop wise and stirred at RT overnight in a seal tube. Reaction mass waspoured in to water, extracted with ethyl acetate and concentrated invacuo. The crude was purified by combi-flash to afford title product asa colourless liquid (0.21 g, 500%).

¹H NM/R (400 MHz, DMSO-d6) δ 8.46 (dd, J₁=2.0 Hz, J₂=4.0 Hz, 1H), 7.85(dd, J₁=2.0 Hz, J₂=7.6 Hz, 1H), 7.44-7.40 (m, 2H), 7.05 (dd, J₁=3.6 Hz,J₂=7.2 Hz, 1H), 6.94-6.90 (m, 2H), 3.44 (s, 3H), 3.29 (s, 3H), LC-MS:m/z 321.0 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-V using appropriate reactants and reagents and in presenceof suitable solvents and appropriate reaction conditions.

Intermediate CP No. Reactant Structure Analytical data 241 V.1 II.9

¹H NMR (400 MHz, DMSO- d6) δ8.49-8.48 (m, 1H), 7.89- 7.87 (m, 1H),7.21-7.14 (m, 2H), 7.11-7.07 (m, 2H), 6.94- 6.91 (m, 1H), 3.43 (s, 3H),3.32 (s, 3H). LC-MS: m/z 321.0 (M + H)⁺ 239 V.2 IV.2

¹H NMR (400 MHz, DMSO- d6) δ 7.6 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 6.8Hz, 2H), 3.39 (s, 3H), 3.19 (s, 3H), 1.38 (m, 2H), 1.07 (s, 2H). 252 V.3II.4

¹H NMR (400 MHz, DMSO- d6) δ 8.19 (d, J = 1.6 Hz, 1H), 7.92 (dd, J₁ =1.6 Hz, J₂ = 8.0 Hz, 1H), 7.72-7.63 (m, 1H), 7.57 (s, 1H), 7.52-7.47 (m,2H), 3.62 (s, 3H), 3.30 (s, 3H). LC-MS: m/z 323.9 (M + H)²⁺ 255 V.4II.20

¹H NMR (400 MHz, DMSO- d6) δ 7.90-7.80 (m, 1H), 7.80- 7.70 (m, 1H), 7.65(d, J = 9.6 Hz, 2H), 7.50-7.40 (m, 2H), 6.48 (d, J = 9.2 Hz, 2H), 3.56(s, 3H), 3.25 (s, 3H), 1.50 (s, 9H). LC-MS: m/z 342.1 (M + H)⁺ 258 V.5II.15

¹H NMR (400 MHz, DMSO- d6) δ 8.57 (dd, J₁ = 2.0 Hz, J₂ = 4.9 Hz, 1H),8.00 (dd, J₁ = 1.9 Hz, J₂ = 7.8 Hz, 1H), 7.73 (d, J = 9.3 Hz, 2H), 7.23(m, 1H), 6.89 (d, J = 8.8 Hz, 2H), 3.45 (s, 3H), 3.32 (s, 3H), 1.52 (s,9H). 317 V.6 IV.4

LC-MS: m/z 344.9 (M + H)⁺² 353 V.7 II.25

¹H NMR (400 MHz, DMSO- d6) δ 7.79 (d, J = 7.2 Hz, 1H), 7.68 (t, J = 8.0Hz, 1H), 7.43- 7.36 (m, 2H), 7.25-7.21 (m, 2H), 7.04 (s, 1H), 6.75 (d, J= 6.8 Hz, 1H), 3.54 (s, 3H), 3.22 (s, 3H), 1.49 (s, 9H). LC- MS: m/z342.1 (M + H)⁺ 340 V.8 Int-IV

¹H NMR (400 MHz, DMSO- d6) δ 7.67 (d, J = 7.6 Hz, 1H), 7.60-7.58 (m,1H), 7.52 (d, J = 8.0 Hz, 1H), 7.38-7.36 (m, 3H), 7.08 (d, J = 8.0 Hz,2H), 3.78 (s, 3H), 3.29 (s, 3H). LC- MS: m/z 348.0 (M + H)⁺ 357 V.9II.32

¹H NMR (400 MHz, DMSO- d6) δ 7.69 (d, J = 8.0 Hz, 1H), 7.65-7.60 (m,1H), 7.39-7.30 (m, 3H), 7.15-7.07 (m, 3H), 6.94 (d, J = 8.8 Hz, 2H),6.76 (d, J = 8.0 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 3.56 (s, 3H), 3.22(s, 3H), 3.18 (s, 3H), 2.03 (s, 9H), 1.64 (s, 6H). 318 V.10 Int-II

LC-MS: m/z 367.9 (M + H)⁺

Intermediate-VI

Step-a: Synthesis of methyl2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)amino) phenyl) amino) benzoate(Intermediate-VI)

A solution of Intermediate-II (0.5 g, 1.63 mmol, 1.0 eq.) andIntermediate-I.1 (0.37 g, 1.63 mmol, 1.0 eq.) in toluene (10 mL) wasde-gassed with N₂ gas for 15 min. Pd₂dba₃ (0.12 g, 0.13 mmol, 0.08 eq.)and XPhos (0.16 g, 0.326 mmol, 0.2 eq.) were added and de-gassed for 5min. Reaction mass was heated at 110° C. for 16 h. Reaction mass wasfiltered through celite, concentrated in vacuo and purified bycombi-flash to afford the title product as pale yellow solid (0.26 g,35%).

¹H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.02 (s, 1H), 7.86 (dd, J₁=1.4Hz, J₂=7.8 Hz, 1H), 7.35 (t, J=1.4 Hz, 1H), 7.21 (d, J=8.8 Hz, 2H),7.12-6.96 (m, 7H), 6.69 (t, J=6.8 Hz, 1H), 3.85 (s, 3H), 2.04 (s, 3H),1.83 (s, 6H), 1.72 (s, 6H); LC-MS: m/z 452.4 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-VI using appropriate reactants and reagents employingsuitable Pd catalysts and ligands and in presence of suitable solventsand appropriate reaction conditions.

Inter- medi- ate CP No. Reactant Structure Analytical data 64 VI.1Int-II & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 7.86 (dd, J₁ = 2.0 Hz, J₂ =9.8 Hz, 1H), 7.54 (s, 1H), 7.36-7.34 (m, 2H), 7.20 (s, 2H), 7.13 (d, J =8.8 Hz, 2H), 6.06 (s, 1H), 7.03 (d, J = 4.9 Hz, 1H), 7.01 (s, 1H), 6.72(t, J = 6.8 Hz, 1H), 3.85 (s, 3H), 2.05 (bs, 3H), 1.84 (bs, 6H), 1.31(bs, 6H). LC-MS: m/z 487.2 (M + H)⁺ 93 VI.2 Int-II & I.33

¹H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.89-7.87 (dd, J₁ = 2.0 Hz, J₂= 8.4 Hz, 1H), 7.71 (s, 1H), 7.42- 7.23 (m, 6H), 7.21-7.19 (m, 4H),7.15-7.07 (m, 3H), 6.74 (t, J = 7.3 Hz, 1H), 3.86 (s, 3H), 3.06- 3.02(m, 1H), 1.14 (d, J = 12.8 Hz, 6H). LC- MS: m/z 471.1 (M + H)⁺ 113 VI.3Int-II & I.5

¹H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.89-7.87 (dd, J₁ = 1.5 Hz, J₂= 7.9 Hz, 1H), 7.72 (s, 1H), 7.38- 7.37 (m, 2H), 7.29-7.17 (m, 10H),7.08 (d, J = 8.3 Hz, 1H), 6.75 (d, J = 8.3 Hz, 1H), 3.86 (s, 3H), 2.27(s, 3H). LC-MS: m/z 442.4 (M + H)⁺ 115 VI.4 Int-II & I.6

¹H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 7.96 (d, J = 8.3 Hz, 1H), 7.73(d, J = 7.9 Hz, 1H), 7.54 (d, J = 7.3 Hz, 1H), 7.48-7.45 (m, 1H),7.34-7.32 (m, 1H), 7.31 (d, J = 8.8 Hz, 1H), 7.25 (d, J = 3.9 Hz, 1H),7.24- 7.18 (m, 6H), 7.10 (d, J = 9.3 Hz, 1H), 6.72- 6.68 (m, 1H), 6.18(s, 1H), 3.91 (s, 3H). LC- MS: m/z 497.1 (M + H)⁺ 116 VI.5 Int-II & I.7

¹H NMR (400 MHz, DMSO-d6) δ 9.20 (s, 1H), 8.34 (s, 1H), 7.87 (d, J = 6.8Hz, 1H), 7.51 (dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 1H), 7.45 (t, J = 6.4 Hz,1H), 7.36 (t, J = 7.3 Hz, 1H), 7.30-7.25 (m, 3H), 7.17 (s, 4H), 7.11 (d,J = 8.8 Hz, 2H), 7.04 (d, J = 8.4 Hz, 1H), 6.73 (t, J = 7.3 Hz, 1H),3.85 (s, 3H). 118 VI.6 Int-II & I.8

¹H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.89-7.87 (dd, J₁ = 1.5 Hz, J₂= 7.9 Hz, 1H), 7.71 (s, 1H), 7.53 (d, J = 1.9 Hz, 1H), 7.41- 7.36 (m,1H), 7.34-7.29 (dd, J₁ = 1.9 Hz, J₂ = 8.3 Hz, 3H), 6.24 (d, J = 8.3 Hz,1H), 7.21-7.15 (m, 4H), 7.09 (t, J = 9.3 Hz, 2H), 7.01 (t, J = 7.4 Hz,1H), 6.76-6.72 (dd, J₁ = = 1.0 Hz, J₂ = 8.3 Hz, 1H), 3.86 (s, 3H), 3.79(s, 3H). LC-MS: m/z 458.3 (M + H)⁺ 121 VI.7 Int-II & I.9

¹H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.91-7.87 (m, 1H), 7.69 (s,1H), 7.50 (d, J = 8.8 Hz, 1H), 7.38- 7.36 (m, 1H), 7.30-7.06 (m, 8H),6.99-6.96 (dd, J₁ = 2.0 Hz, J₂ = 8.3 Hz, 1H), 6.88-6.80 (m, 1H), 6.74(t, J = 6.8 Hz, 1H), 3.86 (s, 3H), 2.03 (s, 6H). LC-MS: m/z 457.1 (M +H)⁺ 122 VI.8 Int-II & I.10

¹H NMR (400 MHz, DMSO-d6) δ 9.24 (s, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.78(s, 1H), 7.55 (d, J = 7.3 Hz, 1H), 7.49 (s, 1H), 7.43-7.37 (m, 4H), 7.26(s, 2H), 7.21 (s, 4H), 7.1 (d, J = 8.3 Hz, 1H), 6.75 (t, J = 7.3 Hz,1H), 3.86 (s, 3H). LC-MS: m/z 463.1 (M + H)⁺ 125 VI.9 Int-I

LC-MS: m/z 396.3 (M + H)⁺ 126 VI.10 Int-II & I.11

¹H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 7.87 (d, J = 1.5 Hz, 1H), 7.62(s, 1H), 7.35 (t, J = 6.8 Hz, 1H), 7.29- 7.06 (m, 11H), 6.73 (t, J = 7.3Hz, 1H), 3.86 (s, 3H), 2.05 (s, 3H), 1.90 (s, 3H). LC-MS: m/z 457.1 (M +H)⁺ 135 VI.11 Int-II

¹H NMR (400 MHz, DMSO-d6) δ 9.39 (s, 1H), 8.26 (s, 1H), 7.99- 7.92 (m,4H), 7.70 (d, J = 8.4 Hz, 2H), 7.55-7.46 (m, 4H), 7.38-7.33 (m, 2H),6.89 (t, J = 8.0 Hz, 1H), 3.87 (s, 3H). LC- MS: m/z 387.0 (M + H)⁺ 140VI.12 Int-II & I.12

¹H NMR (400 MHz, DMSO-d6) δ 9.19 (s, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.65(s, 1H), 7.43 (s, 1H), 7.36 (t, J = 6.8 Hz, 1H), 7.27 (d, J = 6.8 Hz,1H), 7.19-7.03 (m, 6H), 6.74 (t, J = 7.3 Hz, 1H), 5.92 (s, 1H), 3.85 (s,3H), 2.35 (m, 2H), 1.75 (m, 4H), 0.99 (m, 6H). LC-MS: m/z 460.3 (M + H)⁺141 VI.13 II.28 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 2H), 8.02 (s, 1H), 7.87 (dd, J₁ =1.2 Hz, J₂ = 4.8 Hz, 1H), 7.55-7.53 (m, 1H), 7.41-7.38 (m, 2H),7.24-7.19 (m, 2H), 7.12- 7.10 (m, 1H), 3.74 (s, 3H), 2.05 (s, 3H), 1.82(s, 6H), 1.72 (s, 6H), 1.34 (s, 9H). 142 VI.14 II.29 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.28 (s, 1H), 8.05 (d, J = 1.2Hz, 1H), 7.87- 7.85 (m, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.58- 7.54 (m,1H), 7.41-7.38 (m, 2H), 7.32-7.28 (m, 2H), 3.77 (s, 3H), 2.05 (s, 3H),1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 589.1 (M + H)⁺ 144, 152 VI.15II.30 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 7.96 (d, J = 3.2 Hz, 1H), 7.84 (dd, J₁ = 1.2Hz, J₂ = 7.6 Hz, 1H), 7.79 (s, 1H), 7.56 (t, J = 2.0 Hz, 1H), 7.47- 7.46(m, 1H), 7.41-7.35 (m, 3H), 7.27 (dd, J₁ = 1.2 Hz, J₂ = 8.0 Hz, 1H),7.21 (d, J = 2.8 Hz, 1H), 7.15 (d, J = 8.0 Hz, 1H), 3.75 (s, 3H), 2.04(s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.32 (s, 9H). LC- MS: m/z 588.1(M + H)⁺ 158 VI.16 II.6 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 8.17 (s, 1H), 7.37-7.04 (m, 12H), 3.82 (bs,3H), 2.04 (s, 3H), 1.85 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 487.1 (M + H)⁺170 VI.17 I.4

¹H NMR (400 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.41 (dd, J₁ = 2.0 Hz, J₂ =4.4 Hz, 1H), 8.35 (d, J = 8.8 Hz, 1H), 8.30 (dd, J₁ = 2.0 Hz, J₂ = 8.0Hz, 1H), 7.56 (d, J = 2.0 Hz, 1H), 7.37 (dd, J₁ = 1.6 Hz, J₂ = 8.8 Hz,1H), 6.95 (dd, J₁ = 4.4 Hz, J₂ = 8.0 Hz, 1H), 3.92 (s, 3H), 2.06 (s,3H), 1.86 (s, 6H), 1.74 (s, 6H). 173 VI.18 Int-I

¹H NMR (400 MHz, DMSO-d6) δ 7.43 (d, J = 10.4 Hz, 2H), 7.32 (d, J = 2.0Hz, 1H), 7.18- 7.17 (m, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.4Hz, 2H), 4.1 (m, 1H), 3.61 (d, J = 2.4 Hz, 4H), 2.90 (m, 2H), 2.80 (m,1H), 2.05 (s, 3H), 1.83 (s, 6H), 1.73 (s, 6H), 1.34-1.30 (m, 15H). 175VI.19 II.31 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 8.55 (d, J = 2.8 Hz, 1H), 8.28 (d, J = 6.0Hz, 1H), 7.92 (s, 1H), 7.77 (s, 1H), 7.46- 7.42 (m, 3H), 7.36 (d, J =1.6 Hz, 1H), 7.23 (dd, J₁ = 2.0 Hz, J₂ = 8.8 Hz, 1H), 7.15 (d, J = 8.4Hz, 1H), 3.78 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.34(s, 9H). LC-MS: m/z 589.1 (M + H)⁺ 177 VI.20 I.15

¹H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.41 (dd, J₁ = 2.0 Hz, J₂ =4.9 Hz, 1H), 8.26 (dd, J₁ = 1.9 Hz, J₂ = 7.8 Hz, 1H), 7.68 (d, J = 6.8Hz, 1H), 7.50 (s, 1H), 7.26 (t, J = 7.8 Hz, 1H), 7.05 (d, J = 7.9 Hz,1H), 6.88-6.85 (m, 1H), 3.90 (s, 3H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74(s, 6H). LC-MS: m/z 363.1 (M + H)⁺ 185 VI.21 IIIa & Int-I

LC-MS: m/z 464.3 (M + H)⁺ 187 VI.22 III.1 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 7.77 (s, 1H), 7.33 (s, 1H), 7.18 (s, 2H),7.12 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.78-3.72 (m, 1H),3.56 (s, 3H), 3.43- 3.39 (m, 1H), 3.25-3.21 (m, 1H), 2.89-2.80 (m, 1H),2.38-2.32 (m, 1H), 2.09-2.01 (m, 4H), 1.89- 1.81 (m, 7H), 1.82-1.69 (m,8H). 192 VI.23 III.2 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 7.61 (s, 1H), 7.57 (s, 1H), 7.34 (s, 1H),7.19 (d, J = 0.8 Hz, 2H), 7.10-7.08 (m, 3H), 6.94 (d, J = 8.4 Hz, 2H),5.49 (s, 2H), 4.31- 4.25 (m, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s,6H), 1.28 (t, J = 6.8 Hz, 3H). 197 VI.24 III.4 & Int-I

LC-MS: m/z 464.1 (M + H)⁺ 199 VI.25 IIIb & Int-I

LC-MS: m/z 464.1 (M + H)⁺ 200 VI.26 II.9 & I.15

¹H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H), 8.38 (t, J = 1.4 Hz, 1H),8.25 (d, J = 7.8 Hz, 1H), 8.12 (s, 1H), 7.66 (s, 1H), 7.19-7.11 (m, 3H),7.02 (d, J = 7.8 Hz, 1H), 6.95 (d, J = 7.8 Hz, 1H), 6.89-6.83 (m, 2H),6.70 (d, J = 7.8 Hz, 1H), 3.89 (s, 3H), 2.04 (s, 3H), 1.75 (s, 6H), 1.72(s, 6H). LC-MS: m/z 454.3 (M + H)⁺ 210 VI.27 III.7 & Int-I

¹H NMR (400 MHz, DMSO-d6) +67 7.91 (s, 1H), 7.77 (s, 1H), 7.58 (d, J =8.4 Hz, 1H), 7.37 (d, J = 2.0 Hz, 1H), 7.32 (d, J = 8.8 Hz, 1H), 7.23-7.21 (m, 1H), 6.99 (s, 1H), 6.92 (d, J = 8.0 Hz, 1H), 5.19 (s, 2H), 4.12(q, J = 14 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H), 1.17 (t, J= 6.8 Hz, 3H). LC-MS: m/z 464.2 (M + H)⁺ 213 VI.28 III.8 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 8.38 (s, 1H), 7.85 (s, 1H), 7.64 (s, 1H),7.34 (s, 1H), 7.21 (s, 2H), 7.17 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 8.4Hz, 2H), 5.24 (s, 2H), 4.23-4.17 (q, J = 3.6 Hz, 2H), 2.04 (s, 3H), 1.83(s, 6H), 1.72 (s, 6H), 1.25 (t, J = 7.2 Hz, 3H). 214 VI.29 III.9 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 8.69-8.68 (m, 1H), 8.15-8.13 (m, 1H),7.41-7.39 (m, 2H), 7.30 (d, J = 2.0 Hz, 1H), 7.15-7.14 (m, 2H), 7.12-7.03 (m, 3H), 6.94-6.89 (m, 1H), 4.34 (s, 2H), 3.83 (s, 3H), 2.03 (s,3H), 1.81 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 487.2 (M + H)⁺ 217 VI.30III.10 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 7.54 (s, 1H), 7.32 (s, 1H), 7.24 (t, J = 2.0Hz, 1H), 7.17 (s, 2H), 7.01 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.0 Hz,2H), 6.88-6.87 (m, 1H), 6.15-6.14 (m, 1H), 5.43 (s, 2H), 4.20-4.15 (q, J= 7.2 Hz, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.23 (t, J =6.8 Hz, 3H). LC-MS: m/z 489.2 (M + H)⁺ 218 VI.31 Int-V & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 8.36-8.34 (dd, J₁ = 2.0 Hz, J₂ = 4.8 Hz,1H), 7.71-7.67 (m, 1H), 7.5 (s, 1H), 7.32 (d, J = 1.6 Hz, 1H), 7.22-7.19 (dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 6.95-6.80 (m, 5H), 3.37 (s, 3H), 3.29 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H),1.72 (s, 6H). LC-MS: m/z 502.2 (M +H)⁺ 219 VI.32 III.11 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 7.44 (d, J = 8.0 Hz, 1H), 7.29 (s, 2H), 7.20(d, J = 2.8 Hz, 1H), 7.09-7.06 (m, 3H), 6.87 (dd, J₁ = 1.6 Hz, J₂ = 8.4Hz, 1H), 6.37 (d, J = 2.8 Hz, 1H), 5.11 (s, 2H), 4.16-4.12 (m, 2H), 2.03(s, 3H), 1.81 (d, J = 2.8 Hz, 6H), 1.71 (s, 6H), 1.19 (t, J = 7.2 Hz,3H). LC-MS: m/z 463.2 (M + H)⁺ 220 VI.33 III.12 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 7.93 (d, J = 0.8 Hz, 1H), 7.85 (d, J = 0.8Hz, 1H), 7.67 (s, 1H), 7.34 (s, 1H), 7.19 (t, J = 7.2 Hz, 3H), 6.89 (d,J = 8.4 Hz, 2H), 6.74 (d, J = 8.0 Hz, 1H), 5.17 (s, 2H), 3.72 (s, 3H),2.05 (s, 3H), 1.83 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 476.2 (M + H)⁺ 221VI.34 III.13 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 8.10 (s, 1H), 7.69 (s, 1H), 7.64 (s, 1H),7.34 (d, J = 2.0 Hz, 1H), 7.21-7.13 (m, 3H), 6.85 (d, J = 8.4 Hz, 1H),6.77 (s, 1H), 6.61 (d, J = 8.0 Hz, 1H), 5.45 (s, 2H), 3.73 (s, 3H), 2.05(s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 476.3 (M + H)⁺ 227VI.35 III.14 & Int-I

LC-MS: m/z 463.2 (M + H)⁺ 233 VI.36 II.9 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.38 (dd, J₁ = 2.0 Hz, J₂ =4.9 Hz, 1H), 8.24 (dd, J₁ = 2.0 Hz, J₂ = 7.8 Hz, 1H), 7.56 (s, 1H), 7.48(s, 1H), 7.32 (m, 2H), 7.23 (m, 1H), 7.14 (m, 2H), 6.88 (m, 1H), 6.68(m, 1H), 3.90 (s, 3H), 2.08 (s, 3H), 1.85 (s, 6H), 1.72 (s, 6H). LC-MS:m/z 488.2 (M + H)⁺ 239 VI.37 V.2 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 7.74 (s, 1H), 7.36 (s, 1H), 7.23 (m, 2H),7.1 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.41 (s, 3H), 3.15(s, 3H), 2.05 (bs, 3H), 1.84 (bs, 6H), 1.72 (bs, 6H), 1.3 (m, 2H), 1.05(m, 2H). LC-MS: m/z 493.2 (M + H)⁺ 241 VI.38 V.1 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 8.39 (dd, J₁ = 2.0 Hz, J₂ = 4.8 Hz, 1H),7.79 (dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H), 7.54 (s, 1H), 7.32 (d, J = 2.0Hz, 1H), 7.25 (d, J = 8.4 Hz, 1H), 7.18 (dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz,1H), 7.10 (t, J = 8.0 Hz, 1H), 6.95 (dd, J₁ = 3.2 Hz, J₂ = 7.6 Hz, 1H),6.66 (dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz, 1H), 6.60 (t, J = 2.0 Hz, 1H), 6.46(dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H), 3.39 (s, 3H), 3.31 (s, 3H), 2.04 (s,3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 502.1 (M + H)⁺ 243 VI.39II.13 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 8.29 (dd, J₁ = 2.0 Hz, J₂ = 4.9 Hz, 1H),8.25 (dd, J₁ = 2.0 Hz, J₂ = 7.3 Hz, 1H), 7.54 (s, 1H), 7.34 (s, 1H),7.22 (m, 3H), 7.04 (d, J = 9.3 Hz, 2H), 6.99 (d, J = 9.2 Hz, 2H), 3.86(s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 489.0 (M +H)⁺ 245 VI.40 Int-V & I.1

¹H NMR (400 MHz, DMSO-d6) δ 8.33 (dd, J₁ = 2.0 Hz, J₂ = 4.8 Hz, 1H),7.97 (s, 1H), 7.65 (dd, J₁ = 2.0 Hz, J₂ = 7.2 Hz, 1H), 7.2 (d J = 8.8Hz, 2H), 6.97-6.94 (m, 4H), 6.89-6.82 (m, 3H), 3.35 (s, 3H), 3.27 (s,3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 468.1 (M + H)⁺247 VI.41 II.9 & I.1

¹H NMR (400 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.41 (dd, J₁ = 2.0 Hz, J₂ =4.4 Hz, 1H), 8.25 (dd, J₁ = 1.9 Hz, J₂ = 7.8 Hz, 1H), 8.05 (s, 1H), 7.56(t, J = 2.0 Hz, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.15 (t, J = 7.8 Hz, 1H),7.13 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 8.8 Hz, 1H), 6.88 (m, 1H), 6.71(dd, J₁ = 1.5 Hz, J₂ = 7.8 Hz, 1H), 3.89 (s, 3H), 2.04 (bs, 3H), 1.84(s, 6H), 1.73 (s, 6H). 250 VI.42 III.15 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 7.48 (s, 1H), 7.33 (s, 1H), 7.19 (d, J = 1.0Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 3.57 (s,3H), 3.37 (s, 2H), 2.80-2.78 (m, 1H), 2.64- 2.61 (m, 1H), 2.10-1.99 (m,5H), 1.83-1.72 (m, 14H), 1.63-1.62 (m, 1H), 1.47-1.40 (m, 2H). LC- MS:m/z 493.1 (M + H)⁺ 252 VI.43 V.3 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 8.04 (s, 1H), 7.94 (d, J = 1.6 Hz, 1H), 7.77(dd, J₁ = 1.2 Hz, J₂ = 7.6 Hz, 1H), 7.68-7.64 (m, 2H), 7.48 (d, J = 1.6Hz, 1H), 7.43- 7.35 (m, 2H), 7.30 (d, J = 2.4 Hz, 1H), 7.18 (dd, J₁ =2.0 Hz, J₂ = 8.4 Hz, 1H), 3.55 (s, 3H), 3.31 (s, 3H), 2.04 (s, 3H), 1.82(s, 6H). LC-MS: m/z 503.1 (M + H)⁺ 276, 293 VI.44 Int-II

¹H NMR (400 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.69 (s, 1H), 7.88 (dd, J₁ =1.4 Hz, J₂ = 7.8 Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.41-7.37 (m, 1H),7.23-7.17 (m, 4H), 7.10 (d, J = 7.9 Hz, 1H), 7.02 (d, J = 8.8 Hz, 2H),6.77-6.73 (m, 1H), 3.75 (s, 3H), 1.51 (s, 9H). 277 VI.45 Int-II & I.16

¹H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.24 (s, 1H), 7.87 (dd, J₁ =1.2 Hz, J₂ = 7.6 Hz, 1H), 7.40-7.28 (m, 3H), 7.20-7.10 (m, 10H), 7.02(d, J = 8.4 Hz, 1H), 6.71 (t, J = 7.6 Hz, 1H), 3.85 (s, 3H), 3.11-3.07(m, 1H), 1.13 (d, J = 2.8 Hz, 6H). LC-MS: m/z 437.1 (M + H)⁺ 287 VI.46Int-II & I.17

¹H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.07 (s, 1H), 7.86 (dd, J₁ =1.2 Hz, J₂ = 7.6 Hz, 1H), 7.37-7.33 (m, 1H), 7.15-7.06 (m, 3H),7.04-6.98 (m, 2H), 6.72- 6.68 (m, 1H), 3.85 (s, 3H), 3.40 (s, 3H), 2.36-2.32 (m, 5H), 1.43-1.30 (m, 5H), 1.29-1.21 (m, 5H), 0.84 (t, J = 7.2 Hz,6H). LC-MS: m/z 460.1 (M + H)⁺ 291 VI.47 IV.3 & I.1

¹H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 7.87 (d, J = 7.2 Hz, 1H),7.7-7.65 (m, 3H), 7.32-7.28 (m, 3H), 7.17- 7.13 (m, 4H), 3.94 (s, 3H),3.8 (s, 3H), 2.06 (s, 3H), 1.83 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 492.1(M + H)⁺ 292 VI.48 Int-II & I.19

¹H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.11 (s, 1H), 7.86 (dd, J₁ =1.5 Hz, J₂ = 7.8 Hz, 1H), 7.33 (t, J = 1.5 Hz, 1H), 7.15-7.07 (m, 8H),7.02-6.98 (m, 3H), 6.72-6.65 (m, 4H), 3.85 (s, 3H), 3.57 (t, J = 7.3 Hz,2H), 1.58-1.51 (m, 2H), 1.36-1.30 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H).LC-MS: m/z 466.1 (M + H)⁺ 295 VI.49 Int-II & I.2

¹H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.02 (s, 1H), 7.86 (dd, J₁ =1.6 Hz, J₂ = 8.0 Hz, 1H), 7.35 (t, J = 8.4 Hz, 1H), 7.21 (d, J = 8.8 Hz,2H), 7.12-7.04 (m, 4H), 7.01-7.69 (m, 3H), 6.69 (t, J = 7.2 Hz, 1H),3.85 (s, 3H), 2.13-2.12 (m, 1H), 1.66 (s, 2H), 1.50-1.32 (m, 8H), 1.17(s, 2H), 0.85 (s, 6H). LC-MS: m/z 481.0 (M + H)⁺ 309 VI.50 V.10 & I.21

¹H NMR (400 MHz, DMSO-d6) δ 7.8 (d, J = 7.6 Hz, 1H), 7.71- 7.61 (m, 1H),7.44-7.35 (m, 6H), 7.28 (d, J = 8.4 Hz, 2H), 6.50 (d, J = 8.4 Hz, 2H),3.56 (s, 3H), 3.23 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H).LC-MS: m/z 476.1 (M + H)⁺ 317 VI.51 V.6 & I.1

¹H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 7.84 (d, J = 7.6 Hz, 1H),7.78-7.71 (m, 3H), 7.35-7.29 (m, 3H), 7.19- 7.13 (m, 4H), 3.91 (s, 3H),3.89 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 492.3(M + H)⁺ 318 VI.52 V.10 & I.22

¹H NMR (400 MHz, DMSO-d6) δ 7.50-7.46 (m, 2H), 7.27 (d, J = 8.8 Hz, 2H),7.19-7.17 (m, 1H), 7.08 (t, J = 7.6 Hz, 1H), 6.80 (d, J = 8.8 Hz, 2H),6.64 (d, J = 8.8 Hz, 2H), 6.37 (d, J = 8.8 Hz, 2H), 5.09-5.06 (m, 1H),4.23-4.20 (m, 2H), 3.64- 3.61 (m, 2H), 3.45 (s, 3H), 3.15 (s, 3H), 2.04(s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 523.3 (M + H)⁺ 323 VI.53Int-II & I.26

¹H NMR (400 MHz, DMSO-d6) δ 9.11 (s, 1H), 7.86-7.83 (m, 2H), 7.34 (t, J= 7.6 Hz, 1H), 7.07 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H),6.96-6.92 (m, 3H), 6.85 (d, J = 8.8 Hz, 2H), 6.68 (t, J = 7.2 Hz, 1H),3.85 (s, 3H), 3.48 (s, 2H), 1.99 (s, 3H), 1.74-1.63 (m, 13H). LC-MS: m/z483.3 (M + H)⁺ 327 VI.54 II.23 & I.16

¹H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.04 (s, 1H), 7.72- 7.67 (m,3H), 7.37 (t, J = 6.4 Hz, 2H), 7.29 (t, J = 6.4 Hz, 1H), 7.18 (t, J =6.8 Hz, 1H), 7.11- 6.97 (m, 8H), 4.34-4.29 (m, 2H), 3.13-3.08 (m, 1H),1.34 (t, J = 7.2 Hz, 3H), 1.12 (d, J = 6.8 Hz, 6H). LC-MS: m/z 452.3(M + H)⁺ 328 VI.55 IV.5 & I.1

¹H NMR (400 MHz, DMSO-d6) δ 6 8.44 (s, 1H), 7.93-7.91 (m, 1H), 7.72-7.67(m, 1H), 7.45 (t, J = 2.0 Hz, 1H), 7.4 (t, J = 7.6 Hz, 1H), 7.33 (t, J =8.0 Hz, 1H), 7.28- 7.27 (m, 2H), 7.23-7.17 (m, 2H), 7.12-7.1 (m, 2H),3.94 (s, 3H), 3.78 (s, 3H), 2.08 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H).LC-MS: m/z 492.3 (M + H)⁺ 337 VI.56 V.10 & I.27

LC-MS: m/z 536.3 (M + H)⁺ 340 VI.57 V.8 & I.1

¹H NMR (400 MHz, DMSO-d6) δ 8.23 (bs, 1H), 7.70-7.59 (m, 2H), 7.47 (d, J= 7.2 Hz, 1H), 7.4-7.3 (m, 1H), 7.23 (d, J = 8.4 Hz, 2H), 6.99 (d, J =8.0 Hz, 4H), 6.72 (bs, 2H), 3.73 (s, 3H), 3.28 (s, 3H), 2.04 (s, 3H),1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 495.3 (M + H)⁺ 349 VI.58 Int-IV &I.4

¹H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 8.64 (d, J = 8.3 Hz, 1H),8.24 (s, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.64-7.62 (m, 1H), 7.60 (s, 1H), 7.38-7.37 (m, 2H), 7.21-7.19 (m, 1H), 6.95(d, J = 8.3 Hz, 2H), 3.91 (s, 3H), 2.07 (s, 3H), 1.88 (s, 6H), 1.74 (s,6H). LC-MS: m/z 561.2 (M + H)²⁺ 350 VI.59 Int-IV & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 8.65-8.63 (dd, J₁ = 1.2 Hz,J₂ = 8.4 Hz, 1H), 8.35 (s, 1H), 8.01 (d, J = 1.6 Hz, 1H), 7.81 (d, J =8.8 Hz, 2H), 7.69- 7.64 (m, 1H), 7.45 (d, J = 2.0 Hz, 1H), 7.39 (d, J =8.4 Hz, 1H), 7.34 (d, J = 2.0 Hz, 1H), 7.22- 7.18 (dd, J₁ = 1.2 Hz, J₂ =8.4 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 3.91 (s, 3H), 2.07 (s, 3H), 1.99(s, 6H), 1.74 (s, 6H). LC-MS: m/z 515.1 (M + H)²⁺ 361 VI.60 Int-IV &I.30

¹H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 8.56 (d, J = 8.3 Hz, 1H),8.02 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.68 (t, J = 7.0 Hz,1H), 7.44 (d, J = 8.8 Hz, 2H), 7.24 (t, J = 7.0 Hz, 1H), 7.13 (d, J =8.3 Hz, 2H), 7.07 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 2.07 (s, 3H), 1.89(s, 6H), 1.75 (s, 6H). LC-MS: m/z 482.3 (M + H)¹⁺ 385 VI.61 Int-II.10 &I.19

LC-MS: m/z 467.3 (M + H)⁺ 386 VI.62 II.10

¹H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 8.63 (s, 1H), 8.39 (dd, J₁ =2.0 Hz, J₂ = 4.8 Hz, 1H), 8.24 (dd, J₁ = 2.0 Hz, J₂ = 27.6 Hz, 1H), 7.72(d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.8 Hz, 2H), 7.16 (d, J = 8.8 Hz, 2H),6.98 (d, J = 8.8 Hz, 2H), 6.86 (dd, J₁ = 4.8 Hz, J₂ = 7.6 Hz, 1H), 3.91(s, 3H), 1.52 (s, 9H). LC-MS: m/z 420.1 (M + H)⁺ 388 VI.63 Int-II & I.28

¹H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 7.86 (dd, J₁ = 1.2 Hz, J₂ =7.6 Hz, 1H), 7.55 (s, 1H), 7.37-7.26 (m, 1H), 7.25-7.19 (m, 3H), 7.11(d, J = 8.4 Hz, 2H), 7.04 (d, J = 2.8 Hz, 1H), 7.0-6.96 (m, 3H), 6.91-6.85 (m, 4H), 6.70 (t, J = 6.8 Hz, 1H), 3.63 (t, J = 7.2 Hz, 3H),1.56-1.5 (m, 2H), 1.36-1.3 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H). LC-MS: m/z500.2 (M + H)⁺ 389 VI.64 II.10 & I.28

¹H NMR (400 MHz, DMSO-d6) δ 9.91 (s, 1H), 8.35 (dd, J₁ = 2.0 Hz, J₂ =4.8 Hz, 1H), 8.22 (dd, J₁ = 2.0 Hz, J₂ = 7.6 Hz, 1H), 7.53 (d, J = 8.8Hz, 2H), 7.44 (s, 1H), 7.24-7.20 (m, 2H), 7.16 (d, J = 8.8 Hz, 1H), 7.05(d, J = 2.4 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 3.61 (t, J= 7.2 Hz, 2H), 1.56-1.52 (m, 2H), 1.36-1.30 (m, 2H), 0.88 (t, J = 7.2Hz, 3H). LC-MS: m/z 501.2 (M + H)⁺ 127 VI. 65 II.2 & Int-I

¹H NMR (400 MHz, DMSO-d6) δ 10.16 (s, 1H), 8.41 (s, 1H), 8.34 (d, J =8.8 Hz, 1H), 8.05 (d, J = 5.6 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.70(d, J = 8.8 Hz, 1H), 7.43- 7.39 (m, 2H), 7.32-07.30 (m, 1H), 7.08 (t, J= 8.0 Hz, 1H), 6.32 (d, J = 6.0 Hz, 1H), 3.83 (s, 3H), 2.07 (s, 3H),1.88 (s, 6H), 1.74 (s, 6H).

Intermediate-VII

Step-d: Synthesis of4-((3R,5R)-adamantan-1-yl)-2-chloro-N-(4-nitrophenyl) aniline(Intermediate-VII)

A solution of Intermediate-I (8.5 g, 32.5 mmol, 1 eq.) and4-bromonitrobenzene (6.57 g, 32.5 mmol, 1 eq.) in toluene (100 mL) wasde-gassed by bubbling Nitrogen gas for 5 minutes. Cesium carbonate (16g, 48.9 mmol, 1.5 eq.) was added followed by Palladium acetate (0.72 g,3.25 mmol, 0.1 eq.) and XPhos (2.32 g, 4.88 mmol, 0.15 eq.) andde-gassed again for 5 min. Reaction mixture was heated at 110° C. understirring for 16 h. Reaction mixture was cooled to RT, diluted with ethylacetate and filtered through celite. The organic layer was adsorbed oversilica and purified by flash column chromatography. Desired product waseluted in 5 to 10% ethyl acetate in hexanes. Concentrated in vacuo toafford dark yellow oil (7 g, 57%).

¹H NMR (400 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.09-8.07 (m, 2H), 7.44 (s,1H), 7.38 (s, 2H), 6.83-6.79 (m, 2H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74(s, 6H); LC-MS: m/z 383.2 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-VII using appropriate reactants and reagents employingsuitable Pd catalysts and ligands and in presence of suitable solventsand appropriate reaction conditions.

Intermediate CP No. Structure Analytical data 58, 59, 60, 61, 266 VII.1

LC-MS: m/z 415.05 (M − H)⁻. 62 VII.2

n/a 66, 128, 129, 211 VII.3

LC-MS: m/z 449.1 (M − H)⁻ 67, 275 VII.4

¹H NMR (400 MHz, DMSO- d6) δ 9.06 (s, 1H), 8.15 (d, J = 2.8 Hz, 1H),7.66 (dd, J₁ = 2.8 Hz, J₂ = 8.8 Hz, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.23(d, J = 8.8 Hz, 2H), 6.75 (d, J = 8.8 Hz, 1H), 2.03 (s, 3H), 1.82 (s,6H), 1.71 (s, 6H). 132, 133 VII.5

¹H NMR (400 MHz, DMSO- d6) δ 9.00 (s, 1H), 8.10 (d, J = 9.2 Hz, 2H),7.55-7.50 (m, 2H), 7.37-7.28 (m, 5H), 6.96 (d, J = 9.2 Hz, 2H), 2.28 (s,3H). LC-MS: m/z 339.5 (M + H)⁺ 106, 145 VII.6

¹H NMR (400 MHz, DMSO- d6) δ 8.34 (s, 1H), 7.76 (d, J = 8.8 Hz, 2H),7.43 (s, 1H), 7.34-7.33 (m, 2H), 6.87 (d, J = 8.8 Hz, 2H), 4.24 (m, 2H),2.04 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H), 1.28 (t, J = 6.8 Hz, 3H).LC-MS: m/z 410.1 (M + H)⁺ 169 VII.7

LC-MS: m/z 426.2 (M + H)⁺ 191 VII.8

¹H NMR (400 MHz, DMSO- d6) δ 9.25 (s, 1H), 8.09 (d, J = 9.3 Hz, 2H),7.32 (t, J = 7.8 Hz, 1H), 7.17 (s, 1H), 7.12- 7.07 (m, 2H), 7.03 (d, J =9.3 Hz, 2H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 349.1(M + H)⁺ 204, 261 VII.9

LC-MS: m/z 383.0 (M + H)⁺ 249 VII.10

LC-MS: m/z 397.0 (M + H)⁺ 271 VII.11

¹H NMR (400 MHz, DMSO- d6) δ 8.60 (s, 1H), 8.32 (d, J = 2.8 Hz, 1H),8.19 (dd, J₁ = 2.8 Hz, J₂ = 9.2 Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.24(d, J = 8.4 Hz, 2H), 6.98 (d, J = 9.2 Hz, 1H), 2.07 (s, 3H), 1.89 (s,6H), 1.75 (s, 6H). LC- MS: m/z 415.05 (M − H)⁻ 272 VII.12

¹H NMR (400 MHz, DMSO- d6) δ 9.86 (s, 1H), 8.18 (d, J = 9.3 Hz, 2H),8.04 (dd, J₁ = 1.4 Hz, J₂ = 8.3 Hz, 1H), 7.53-7.45 (m, 2H), 7.23 (s,2H), 6.96 (t, J = 6.9 Hz, 1H), 3.93 (s, 3H). 289, 311, 379 VII.13

¹H NMR (400 MHz, DMSO- d6) δ 8.05 (dd, J₁ = 2.0 Hz, J₂ = 7.4 Hz, 2H),7.48 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.3 Hz, 2H), 6.74 (dd, J₁ = 2.0Hz, J₂ = 7.4 Hz, 2H), 3.36 (s, 3H), 2.80 (s, 3H), 1.89 (s, 6H), 1.75 (s,6H). LC-MS: m/z 363.1 (M + H)⁺ 297, 300 VII.14

¹H NMR (400 MHz, DMSO- d6) δ 8.75 (s, 1H), 7.58 (t, J = 7.6 Hz, 1H),7.33-7.27 (m, 3H), 6.83 (d, J = 8.4 Hz, 1H), 6.54 (d, J = 8.8 Hz, 2H),4.76 (s, 2H), 4.33-4.26 (m, 2H), 1.32 (t, J = 7.6 Hz, 3H). LC-MS: m/z258.1 (M + H)⁺ 298, 299 VII.15

¹H NMR (400 MHz, DMSO- d6) δ 10.58 (s, 1H), 8.55 (dd, J₁ = 2.0 Hz, J₂ =4.8 Hz, 1H), 8.35 (dd, J₁ = 2.0 Hz, J₂ = 7.6 Hz, 1H), 8.24-8.20 (m, 2H),8.05-8.01 (m, 2H), 7.10 (dd, J₁ = 4.4 Hz, J₂ = 7.6 Hz, 1H), 3.93 (s,3H). LC-MS: m/z 274.10 (M + H)⁺ 319 VII.16

¹H NMR (400 MHz, DMSO- d6) δ 9.22 (s, 1H), 8.06 (dd, J₁ = 2.0 Hz, J₂ =7.6 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.8 Hz, 2H), 7.00(d, J = 9.2 Hz, 2H), 2.14 (m, 1H), 1.69 (s, 2H), 1.53-1.36 (m, 8H), 1.19(s, 2H), 0.86 (s, 6H). LC-MS: m/z 377.1 (M + H)⁺ 320 VII.17

¹H NMR (400 MHz, DMSO- d6) δ 9.40 (s, 1H), 8.07 (d, J = 9.3 Hz, 2H),7.24 (m, 2H), 7.18 (d, J = 8.8 Hz, 2H), 7.00 (m, 4H), 6.96-6.91 (m, 3H),3.60 (m, 2H), 1.60 (m, 2H), 1.40-1.35 (m, 2H), 0.88 (t, J = 7.4 Hz, 3H).338 VII.18

¹H NMR (400 MHz, DMSO- d6) δ 9.48 (s, 1H), 8.12 (d, J = 9.2 Hz, 2H),7.80 (d, J = 8.8 Hz, 2H), 7.46 (s, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.15(d, J = 8.8 Hz, 2H), 2.06 (s, 9H), 1.65 (s, 6H). LC-MS: m/z 392.1 (M +H)⁺ 352 VII.19

LC-MS: m/z 349.1 (M + H)⁺ 378 VII.20

LC-MS: m/z 349.2 (M + H)⁺ 271 VII.21

LC-MS: m/z 431.15 (M + H)⁺ 521, 541, 605, 606, 607, 608, VII.22

LC-MS: m/z 283.1 (M + H)+ 613, 648 522, 536, 558 VII.23

LC-MS: m/z 297.2 (M + H)+ 528 VII.24

LC-MS: m/z 339.0 (M − H)− 535 VII.25

1H NMR (400 MHz, DMSO- d6): δ 9.36 (s, 1H), 8.10 (d, J = 9.2 Hz, 2H),7.42 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 9.2 Hz,2H). 537 VII.26

LC-MS: m/z 367.2 (M + H)+ 538 VII.27

1H NMR (400 MHz, DMSO- d6) δ 9.22 (s, 1H), 8.06 (dd, J1 = 2 Hz & J2 =7.6 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.15 (dd, J1 = 1.6 Hz & J2 = 6.4Hz, 2H), 6.99 (dd, J1 = 2 Hz & J2 = 7.2 Hz, 2H), 271-2.69 (m, 1H), 2.33(brs, 1H), 2.27 (brs, 1H), 1.73-1.70 (m, 1H), 1.55- 1.46 (m, 4H),1.35-1.29 (m, 2H), 1.16-1.14 (m, 1H). LC- MS: m/z 309.1 (M + H)+. 542VII.28

LC-MS: m/z 283.0 (M + H)+ 545 VII.29

LC-MS: m/z 245.1 (M + H)+ 547 VII.30

1H NMR (400 MHz, DMSO- d6): δ 9.08 (s, 1H), 8.03 (d, J = 9.2 Hz, 2H),7.12 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 9.2 Hz,2H), 3.75-3.73 (m, 4H), 3.10-3.08 (m, 4H). LC-MS: m/z 300.1 (M + H)+.548 VII.31

1H NMR (400 MHz, DMSO- d6): δ 9.41 (s, 1H), 8.11 (d, J = 9.2 Hz, 2H),7.38-7.32 (m, 4H), 7.10 (d, J = 9.2 Hz, 2H). LC-MS: m/z 297.1 (M − H)−549 VII.32

LC-MS: m/z 315.2 (M + H)+ 551 VII.33

LC-MS: m/z 363.1 (M + H)+ 553 VII.34

1H NMR (400 MHz, DMSO- d6): δ 9.17 (s, 1H), 8.06 (d, J = 9.2 Hz, 2H),7.21 (d, J = 8.8 Hz, 2H), 7.10 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz,2H), 4.75 (q, J = 9.2 Hz, 2H). 554, 567 VII.35

LC-MS: m/z 241.2 (M − H)− 555, 556, 574, 583, 584, 552, VII.36

LC-MS: m/z 312.2 (M + H)+ 557, 582, 593 560, 579, 580, 614, 619, 620,621, 625, VII.37

LC-MS: m/z 311.1 (M + H)+ 627, Also for CP compounds 630, 631, 628, 632,633, 634, 635, 636, 637, 640, 629 653, 656, 657, 678, 679 563 VII.38

1H NMR (400 MHz, DMSO- d6): δ 9.43 (s, 1H), 8.03 (d, J = 10 Hz, 1H),7.64 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.08-7.06 (m, 2H),2.53 (s, 3H). 565 VII.39

LC-MS: m/z 327.0 (M + H)+ 568 VII.40

LC-MS: m/z 328.95 (M − H)− 571 VII.41

LC-MS: m/z 355.1 (M + H)+ 572 VII.42

LC-MS: m/z 298.95 (M − H)−. 573 VII.43

LC-MS: m/z 357.0 (M − H)−. 576 VII.44

LC-MS: m/z 284.0 (M + H)+ 577 VII.45

LC-MS: m/z 323.3 (M + H)+ 578 VII.46

LC-MS: m/z 298.2 (M + H)+ 581 VII.47

LC-MS: m/z 296.0 (M + 2)+ 585 VII.48

LC-MS: m/z 327.1 (M + H)+ 588 VII.49

LC-MS: m/z 289.95 (M + H) 589 VII.50

LC-MS: m/z 315.1 (M − H)− 590 VII.51

LC-MS: m/z 311.1 (M − H)− 592 VII.52

LC-MS: m/z 316.9 (M + H)+ 594 VII.53

LC-MS: m/z 332.1 (M − H) − 595 VII.54

LC-MS: m/z 342.0 (M + H) + 596 VII.55

LC-MS: m/z 335.0 (M + H) + 597 VII.56

LC-MS: m/z 304.2 (M + H)+ 602 VII.57

LC-MS: m/z 320.0 (M + H)+ 609, 652, 673 VII.58

LC-MS: m/z 312.2 (M + H)+ 612 VII.59

LC-MS: m/z 283.0 (M + H)+ 617 VII.60

LC-MS: m/z 315.0 (M − H)− 618 VII.61

Proceeded with crude/TLC reference 622 VII.62

LC-MS: m/z 315.0 (M + H)+ 624 VII.63

LC-MS: m/z 287.0 (M + H)+ 626 VII.64

LC-MS: m/z 337.2 (M + H)+ 641, 661, 662 VII.65

LC-MS: m/z 363.1 (M1H)− 660, 675, 676 VII.66

LC-MS: m/z 397.1 (M − H)− 598, 643, 654, 655 VII.67

LC-MS: m/z 333.1 (M + H)+ 646 VII.68

LC-MS: m/z 327.1 (M + H)+ 647 VII.69

LC-MS: m/z 313.1 (M + H)+ 659 VII.70

LC-MS: m/z 332.1 (M + H)+ 663 VII.71

LC-MS: m/z 338.2 (M + H)+ 671, 680, 681 VII.72

LC-MS: m/z 345.1 (M + H)+ 682, 677 VII.73

LC-MS: m/z 331.1 (M + H)+

The below intermediates were prepared by a procedure similar toIntermediate-V using appropriate reactants and reagents employingsuitable Pd catalysts and ligands and in presence of suitable solventsand appropriate reaction conditions.

Intermediate CP No. Reactant Structure Analytical data 249 VII.74 VII

LC-MS: m/z 397.0 (M + H)⁺ 289, 311, 379 VII.75 VII.17

¹H NMR (400 MHz, DMSO-d6) δ 8.05 (dd, J₁ = 2.0 Hz, J₂ = 7.4 Hz, 2H),7.48 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.3 Hz, 2H), 6.74 (dd, J₁ = 2.0Hz, J₂ = 7.4 Hz, 2H), 3.36 (s, 3H), 2.80 (s, 3H), 1.89 (s, 6H), Also forCP compounds 453, 472, 1.75 (s, 6H). LC-MS: 473, 525, 526 m/z 363.1 (M +H)⁺ 271 VII.76 VII.10

LC-MS: m/z 431.15 (M + H)⁺ 521, 541, 605, 606, 607, 608, VII.77 VII.19

LC-MS: m/z 297.1 (M + H)⁺. 613, 648 522, 536, 558 VII.78 VII.20

LC-MS: m/z 311.1 (M + H)⁺ 528 VII.79 VII.21

LC-MS: m/z 355.1 (M + H)⁺ 535 VII.80 VII.22

¹H NMR (400 MHz, DMSO-d₆): δ 8.06 (d, J = 9.2 Hz, 2H), 7.55 (d, J = 8.8Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 6.81 (d, J = 9.2 Hz, 2H), 3.37 (s,3H). 537 VII.81 VII.23

LC-MS: m/z 381.2 (M + H)⁺ 538 VII.82 VII.24

¹H NMR (400 MHz, DMSO-d₆): δ 8.03 (dd, J₁ = 2.4 Hz & J₂ = 7.6 Hz, 2H),7.33 (d, J = 8.4 Hz, 2H), 7.23-7.20 (m, 2H), 6.72 (dd, J₁ = 2 Hz & J₂ =7.6 Hz, 2H), 3.35 (s, 3H), 2.79-2.75 (m, 1H), 2.34-2.31 (m, 2H),1.76-1.73 (m, 1H), 1.56-1.50 (m, 4H), 1.36-1.16 (m, 3H). LC-MS: m/z323.2 (M + H)⁺ 542 VII.83 VII.25

LC-MS: m/z 297.1 (M + H)⁺ 545 VII.84 VII.26

LC-MS: m/z 259.1 (M + H)⁺ 547 VII.85 VII.27

¹H NMR (400 MHz, DMSO-d₆): δ 8.02 (d, J = 9.6 Hz, 2H), 7.16 (d, J = 8.8Hz, 2H, 7.04 (d, J = 8.8 Hz, 2H), 6.67 (d, J = 9.6 Hz, 2H), 3.76-3.74(m, 4H), 3.32 (s, 3H), 3.16-3.13 (m, 4H). LC-MS: m/z 314.2 (M + H)⁺ 548VII.86 VII.28

¹H NMR (400 MHz, DMSO-d₆): δ 8.07 (d, J = 9.2 Hz, 2H), 7.48- 7.45 (m,4H), 6.81 (d, J = 9.2 Hz, 2H), 3.39 (s, 3H). LC-MS: m/z 313.1 (M + H)⁺549 VII.87 VII.29

LC-MS: m/z 329.2 (M + H)⁺. 551 VII.88 VII.30

LC-MS: m/z 377.3 (M + H)⁺. 552 VII.89 VII.33

LC-MS: m/z 345.1 (M + H)⁺. 553 VII.90 VII.31

LC-MS: m/z 327.1 (M + H)⁺. 554, 567 VII.91 VII.32

LC-MS: m/z 257.2 (M + H)⁺. 555 VII.92 VII.33

LC-MS: m/z 312.2 (M + H)⁺. 556 VII.93 VII.33

LC-MS: m/z 241.2 (M − H)⁻ 557 VII.94 VII.33

LC-MS: m/z 312.2 (M + H)⁺ 560, 579, 580, 614, 619, 620, 621, 625, 627VII.95 VII.34

LC-MS: m/z 325.2 (M + H)⁺ Also for CP compounds 628, 629, 630, 631, 632,633, 634, 635, 636, 637, 640, 653, 656, 657, 678, 679 563 VII.96 VII.35

LC-MS: m/z 311.05 (M + H)⁺ 565 VII.97 VII.36

LC-MS: m/z 341.0 (M + H)⁺ 568 VII.98 VII.37

¹H NMR (400 MHz, DMSO-d₆): δ 7.98- 7.94 (m, 1H), 7.31 (d, J = 8.8 Hz,2H), 7.19 (d, J = 8.8 Hz, 2H), 6.57 (dd, J₁ = 2.0 Hz & J₂ = 14.8 Hz,1H), 6.42 (dd, J₁ = 2.0 Hz & J₂ = 9.2 Hz, 1H), 4.82 (q, J = 8.8 Hz, 2H),3.34 (s, 3H). 571 VII.99 VII.38

LC-MS: m/z 369.1 (M + H)⁺ 572 VII.100 VII.39

LC-MS: m/z 315.1 (M + H)⁺ 573 VII.101 VII.40

LC-MS: m/z 357.0 (M − H)⁻ 574, 583, 584 VII.102 VII.33

LC-MS: m/z 284.0 (M + H)⁺ 576 VII.103 VII.41

LC-MS: m/z 298 (M + H)⁺ 577 VII.104 VII.42

LC-MS: m/z 337.2.0 (M + H)⁺ 578 VII.105 VII.43

LC-MS: m/z 312.2 (M + H)⁺ 581 VII.106 VII.44

LC-MS: m/z 310.1 (M + H)⁺ 582 VII.107 VII.33

LC-MS: m/z 324.2 (M + H)⁺ 585 VII.108 VII.45

LC-MS: 342.1 m/z (M + H)⁺ 588 VII.109 VII.46

LC-MS: m/z 304.1 (M + H)⁺ 589 VII.110 VII.47

LC-MS: m/z 331.1 (M − H)⁻ 590 VII.111 VII.48

LC-MS: m/z 327.1 (M − H)⁻ 592 VII.112 VII.49

LC-MS: m/z 331.0 (M − H)⁻ 593 VII.113 VII.33

LC-MS: m/z 337.1 (M + H)⁺ 594 VII.114 VII.50

LC-MS: m/z 346.0 (M + H)⁺ 595 VII.115 VII.51

LC-MS: m/z 356.1 (M − H)⁻ 597 VII.116 VII.53

LC-MS: m/z 318.1 (M + H)⁺ 602 VII.117 VII.54

LC-MS: m/z 332.0 (M + H)⁺ 603 VII.118 VII.52

LC-MS: m/z 377.1 (M + H)⁺ 609, 652, 673 VII.119 VII.55

LC-MS: m/z 326.2 (M + H)⁺ 612 VII.120 VII.56

LC-MS: m/z 297.0 (M + H)⁺ 617 VII.121 VII.57

LC-MS: m/z 331.0 (M + H)⁺ 618 VII.122 VII.58

LC-MS: m/z 315.2 (M + H)⁺ 622 VII.123 VII.59

LC-MS: m/z 329.0 (M + H)⁺ 624 VII.124 VII.60

LC-MS: m/z 301.0 (M + H)⁺ 626 VII.125 VII.61

LC-MS: m/z 351.1 (M + H)⁺ 598, 643, 654, 655 VII.126 VII.64

LC-MS: m/z 345.1 (M + H)⁺ 646 VII.127 VII.65

LC-MS: m/z 340.95 (M + H)⁺ 647 VII.128 VII.66

LC-MS: m/z 326.95 (M + H)⁺ 659 VII.129 VII.67

LC-MS: m/z 346.1 (M + H)⁺ 663 VII.130 VII.68

LC-MS: m/z 352.2 (M + H)⁺ 671, 681 VII.131 VII.69

LC-MS: m/z 359.1 (M + H)⁺

Intermediate-VII

Step-a: Synthesis ofN-(4-((3R,5R)-adamantan-1-yl)phenyl)-3-nitrobenzamide(Intermediate-VIII)

The title compound (1.6 g, 960) was synthesized from intermediate-I.1 (1g, 4.4 mmol, 1 eq.) and 3-nitrobenzoyl chloride (0.82 g, 4.4 mmol, 1eq.) using a procedure similar to Intermediate-IV. LC-MS: m/z 377.2(M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-VII using appropriate reactants and reagents and inpresence of suitable solvents and appropriate reaction conditions.

Intermediate CP No. Structure Analytical data  366, 367 VIII.1

¹H NMR (400 MHz, DMSO-d6) δ 10.43 (s, 1H), 8.80 (s, 1H), 8.47-8.40 (m,2H), 7.85 (t, J = 7.6 Hz, 1H), 7.51-7.49 (m, 2H), 7.41-7.39 (m, 1H),2.08 (s, 3H), 1.89 (s, 6H), 1.75 (s, 6H). LC-MS: m/z 411.1 (M + H)⁺ 373VIII.2

LC-MS: m/z 411.05 (M + H)⁺ 395 VIII.3

¹H NMR (400 MHz, DMSO-d6) δ 10.53 (s, 1H), 8.79 (t, J = 2.0 Hz, 1H),8.45-8.39 (m, 2H), 7.84 (t, J = 8.0 Hz, 1H), 7.72-7.69 (m, 2H),7.25-7.21 (m, 2H), 7.06-7.03 (m, 2H), 6.91- 6.90 (m, 2H), 6.88-6.84 (m,1H), 3.67 (t, J = 7.2 Hz, 2H), 1.59-1.53 (m, 2H), 1.36-1.29 (m, 2H),0.88 (t, J = 7.2 Hz, 3H). LC-MS: m/z 390.2 (M + H)⁺ 339 VIII.4

LC-MS: m/z 405.1 (M + H)⁺ 586 VIII.5

LC-MS: m/z 309.1 (M − H)− 642 VIII.6

LC-MS: m/z 339.05 (M + H)+ 649 VIII.7

1H NMR (400 MHz, DMSO-d6) δ 10.57 (s, 1H), 8.45 (s, 1H), 7.93 (d, J =8.0 Hz, 1H), 7.71-7.68 (m, 1H), 7.58 (s, 1H), 7.54-7.44 (m, 3H), 3.86(s, 3H), 2.38 (s, 3H).  665,  666,  669, 672 VIII.8

LC-MS: m/z 359.1 (M + H)⁺

Intermediate-IX

Step-a: Synthesis of(3R,5R)-1-(3-chloro-4-(4-nitrophenoxy)phenyl)adamantane(Intermediate-IX)

A solution of 4-fluoronitrobenzene (0.6 mL, 5.7 mmol) andIntermediate-1.25 (1.5 g, 6.84 mmol, 1.2 eq.) in DMSO (10 mL) was addedwith potassium carbonate (1.57 g, 11.4 mmol, 2 eq.) and allowed to stirat RT overnight. Reaction mass was poured on to cold water and obtainedsolid was filtered and dried to afford title compound as off-white solid(2 g, 910%).

¹H NMR (400 MHz, DMSO-d6) δ 8.26 (d, J=9.3 Hz, 2H), 7.58 (s, 1H), 7.47(d, J=2.0 Hz, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.1 (d, J=8.3 Hz, 2H), 2.07(bs, 2H), 1.89 (s, 6H), 1.7 (s, 6H). LC-MS: m/z 382.0 (M−H)⁻

The below intermediates were prepared by a procedure similar toIntermediate-IX using appropriate reactants and reagents and in presenceof suitable solvents and appropriate reaction conditions.

Intermediate CP No. Reactant Structure Analytical data 270, 314  IX.1 I.30

¹H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.8Hz, 2H), 7.11 (m, 4H), 2.07 (s, 3H), 1.88 (s, 6H), 1.71 (s, 6H). 360 IX.2  I.32

¹H NMR (400 MHz, DMSO-d6) δ 8.31 (d, J = 8.8 Hz, 2H), 7.57 1H),7.44-7.36 (m, 4H), 7.26 (t, J = 7.3 Hz, 1H), 7.19 (t, J = 8.8 Hz, 3H),2.99-2.95 (m, 1H), 1.17 (d, J = 6.8 Hz, 6H). 383, 384  529, 531, IX.3 I.31

¹H NMR (400 MHz, DMSO-d6) δ 8.27-8.23 (m, 2H), 7.58 (d, J = 2.0 Hz, 1H),7.45 (dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H),7.09-7.03 (m, 2H), 2.17-2.14 (m, 1H), 1.72 (s, 2H), 1.55-1.36 (m, 8H),1.20 (s, 2H), 0.87 (s, 6H). 534  IX.4 

LC-MS: m/z 419.0 (M + H)⁺ 540  IX.5 

LC-MS: m/z 576.2 (M + H)⁺. 543, 544  IX-6 

¹H NMR (400 MHz, DMSO-d6) δ 8.35-8.27 (m, 2H), 8.15 (s, 1H), 7.84 (d, J= 8.4 Hz, 2H), 7.24 (d, J = 9.2 Hz, 2H). 546, 550  IX.7 

Proceeded with crude/TLC reference 561, 564  IX.8 

¹H NMR (400 MHz, DMSO- d₆): δ 8.06 (d, J = 9.2 Hz, 1H), 7.56 (d, J = 1.6Hz, 1H), 7.44-7.42 (m, 1H), 7.26 (d, J = 8.4 Hz, 1H), 7.04 (d, J = 2 Hz,1H), 6.81- 6.78 (m, 1H), 2.52 (s, 3H), 2.15 (s, 1H), 1.72-1.19 (m, 12H),0.86-0.84 (m, 6H). 566, 591  IX.9 

LC-MS: m/z 368.0 (M + 2H)⁺ 569, 570  IX.10

Proceeded with crude/TLC reference 575  IX.11

¹H NMR (400 MHz, DMSO- d₆): δ 8.29-8.26 (m, 2H), 7.93 (s, 1H), 7.69 (d,J = 8.4 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.24- 6.96 (m, 3H). 587 IX.12

LC-MS: m/z 338.85 (M + H)⁺ 599  IX.13

LC-MS: m/z 361.3 (M + H)⁺ 600  IX.14

LC-MS: m/z 334.05 (M+)⁺ 601  IX.15

LC-MS: m/z 319.0 (M + H)⁺ 615  IX.16

LC-MS: m/z 377.0 (M + H)⁺ 616  IX.17

LC-MS: m/z 388.0 (M + H)⁺

Intermediate-X

Step-a: Synthesis of (3r,5r,7r)-1-(3-chloro-4-methylphenyl)adamantane(Xa)

A solution of (3r,5r,7r)-1-(p-tolyl)adamantane (2 g, 8.8 mmol) in aceticacid was added with N-chlorosuccinimide in portions for a period of 30minutes. Reaction mass was heated at 75° C. overnight. Reaction mass waspoured on to cold water and obtained solid was filtered off and driedunder vacuum. Title compound was obtained as white solid (2.2 g, 960%).¹H NM/R (400 MHz, DMSO-d6) δ 7.31 (d, J=1.9 Hz, 1H), 7.26-7.22 (m, 2H),2.27 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).

Step-b: Synthesis of(3r,5r,7r)-1-(4-(bromomethyl)-3-chlorophenyl)adamantane (Xb)

A solution of compound Xa (1 g, 3.8 mmol) in carbon tetrachloride (40mL) was added with Bromine (0.61 g, 3.8 mmol) drop wise and Benzoylperoxide (catalytic). Reaction mass was heated to reflux overnight.Concentrated in vacuo and crude was purified by column chromatography toafford title product as off-white solid (0.5 g, 380%). ¹H NMR (400 MHz,DMSO-d6) δ 7.38 (d, J=8.0 Hz, 2H), 7.24 (m, 1H), 4.58 (s, 2H), 2.10 (s,3H), 1.81 (s, 6H), 1.72 (s, 6H).

Step-c: Synthesis of1-(4-((3R,5R)-adamantan-1-yl)-2-chlorobenzyl)-4-nitro-1H-pyrazoleIntermediate-X)

This intermediate was prepared according to a similar proceduredescribed for Intermediate-III by using Intermediate-Xb (0.3 g, 0.88mmol, 1 eq.) and 4-nitropyrazole (0.12 g, 1.06 mmol, 1.2 eq.) to affordtitle product as an off-white solid (0.3 g, 91M). ¹H NMR (400 MHz,DMSO-d6) δ 8.99 (s, 1H), 8.28 (s, 1H), 7.41 (d, J=2.0 Hz, 1H), 7.35 (dd,J₁=1.9 Hz, J₂=8.3 Hz, 1H), 7.21 (d, J=8.3 Hz, 1H), 5.47 (s, 2H), 2.04(s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).

The below intermediates were prepared by a procedure similar toIntermediate-X using appropriate reactants and reagents and in presenceof suitable solvents and appropriate reaction conditions.

Intermediate CP No. Reactant Structure Analytical data 226 XIII.1

¹H NMR (400 MHz, DMSO-d6) δ 9.02 (s, 1H), 7.44 (s, 1H), 7.39 (s, 1H),5.63 (s, 2H), 2.05 (s, 3H), 1.85 (d, J = 2.4 Hz, 6H), 1.72 (s, 6H).LC-MS: m/z 373.2 (M + H)⁺ 228 XIII.2

¹H NMR (400 MHz, DMSO-d6) δ 7.47 (dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H),7.42 (d, J = 1.6 Hz, 1H), 7.34-7.33 (m, 2H), 7.25 (d, J = 8.0 Hz, 1H),7.21 (d, J = 2.0 Hz, 1H), 4.45 (s, 2H), 3.49 (t, J = 8.8 Hz, 2H), 3.07(t, J = 8.0 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS:m/z 423.2 (M + H)⁺ 240 XIII.3

¹H NMR (400 MHz, DMSO-d6) δ 8.39 (d, J = 1.2 Hz, 1H), 7.96 (d, J = 1.6Hz, 1H), 7.44 (d, J = 2.0 Hz, 1H), 7.36-7.35 (m, 1H), 7.22 (d, J = 8.0Hz, 1H), 5.39 (s, 2H), 2.05 (s, 3H), 1.84 (d, J = 2.8 Hz, 6H), 1.72 (s,6H). LC-MS: m/z 372.2 (M + H)⁺ 194 XIII.4 II.8

LC-MS: m/z 480.1 (M + H)⁺ 195 XIII.5 III.3

LC-MS: m/z 494.1 (M + H)⁺

Intermediate-XI

Step-a: Synthesis ofN1-(4-((3R,5R)-adamantan-1-yl)-2-chlorophenyl)benzene-1,4-diamine(Intermediate-XI)

To a solution of Intermediate-VII (7 g, 18.3 mmol, 1 eq.) in THF:water(50 mL+50 mL), ammonium chloride (19.42 g, 36.6 mmol, 20 eq.) followedby Zinc dust (11.91 g, 183 mmol, 10 eq.) were added and stirred at RTfor 16 h. Reaction mixture was diluted with ethyl acetate and filteredthrough celite. The filtrate was washed with water followed by brine.The organic layer was dried over anhydrous Sodium sulfate andconcentrated in vacuo. The crude was washed with n-pentane and dried invacuo to afford desired product as yellow gum (5.9 g, 91%). This wasused in next step without further purification.

¹H NM/R (400 MHz, DMSO-d6) δ 7.20 (d, J=1.9 Hz, 1H) 7.04 (dd, J₁=2.0 Hz,J₂=8.3 Hz, 1H), 6.84 (d, J=8.8 Hz, 2H), 6.78 (s, 1H), 6.72 (d, J=8.8 Hz,1H), 6.54 (d, J=8.8 Hz, 2H), 4.85 (s, 2H), 2.02 (s, 3H), 1.78 (s, 6H),1.70 (s, 6H); LC-MS: m/z 353.1 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-XI using appropriate reactants and reagents and in presenceof suitable solvents and appropriate reaction conditions.

Intermediate CP No. Reactant Structure Analytical data 128 XI.1 VII.3

LC-MS: m/z 421.1 (M + H)⁺  132, 133 XI.2 VII.5

¹H NMR (400 MHz, DMSO- d6) δ 7.25-7.19 (m, 4H), 7.16- 7.14 (m, 1H),7.06-7.02 (m, 2H), 6.91 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.4 Hz, 1H),6.58 (d, J = 8.4 Hz, 2H), 4.93 (s, 2H), 2.24 (s, 3H). LC-MS: m/z 309.0(M + H)⁺ 169 XI.3 VII.7

¹H NMR (400 MHz, DMSO- d6) δ 9.35-8.91 (bs, 1H), 7.80- 7.78 (bs, 1H),7.62-7.57 (m, 2H), 7.45 (d, J = 2.0 Hz, 1H), 7.35 (dd, J₁ = 2.4 Hz, J₂ =8.8 Hz, 1H), 7.01 (d, J = 9.2 Hz, 1H), 2.07 (s, 3H), 1.87 (s, 6H), 1.74(s, 6H). LC-MS: m/z 354.1 (M + H)⁺ 191 XI.4 VII.8

¹H NMR (400 MHz, DMSO- d6) δ 7.34 (s, 1H), 7.02-6.98 (m, 1H), 6.80-6.79(m, 3H), 6.61-6.51 (m, 4H), 4.71 (s, 2H), 2.02 (s, 3H), 1.74 (s, 6H),1.67 (s, 6H). LC-MS: m/z 319.1 (M + H)⁺ 203 XI.5 I.24

¹H NMR (400 MHz, DMSO- d6) δ 7.28 (d, J = 7.8 Hz, 1H), 7.21-7.17 (m,1H), 7.10 (d, J = 3.9 Hz, 2H), 6.88 (t, J = 7.9 Hz, 1H), 6.35 (dd, J₁ =1.5 Hz, J₂ = 8.3 Hz, 1H), 6.27 (m, 2H), 4.91 (s, 2H), 3.86 (s, 2H), 3.13(m, 1H), 1.06 (d, J = 6.9 Hz, 6H). LC-MS: m/z 226.3 (M + H)⁺ 228 XI.6X.2

¹H NMR (400 MHz, DMSO- d6) δ 7.38 (d, J = 1.6 Hz, 1H), 7.36-7.30 (m,2H), 6.69 (d, J = 7.6 Hz, 1H), 5.84 (dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H),5.78 (d, J = 1.2 Hz, 1H), 4.68 (s, 2H), 4.18 (s, 2H), 3.26 (t, J = 8.0Hz, 2H), 2.75 (t, J = 7.6 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s,6H). LC-MS: m/z 393.2 (M + H)⁺  204, 237 261 XI.7 VII.9

¹H NMR (400 MHz, DMSO- d6) δ 7.30 (s, 1H), 7.19 (s, 2H), 7.13 (s, 1H),6.87-6.83 (m, 1H), 6.26 (s, 1H), 6.20 (d, J = 7.8 Hz, 1H), 6.10 (d, J =7.8 Hz, 1H), 4.92 (s, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).LC-MS: m/z 353.1 (M + H)⁺ 232 XI.8 Int-X

LC-MS: m/z 342.2 (M + H)⁺ 226 XI.9 X.1

¹H NMR (400 MHz, DMSO- d6) δ 8.08 (s, 1H), 7.37-7.30 (m, 2H), 7.20-7.10(m, 1H), 5.25 (s, 2H), 5.17 (s, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72(s, 6H). LC-MS: m/z 343.2 (M + H)⁺ 240 XI.10 X.3

¹H NMR (400 MHz, DMSO- d6) δ 7.59 (s, 1H), 7.40-7.38 (m, 1H), 7.34-7.32(m, 1H), 7.15 (d, J = 8.0 Hz, 1H), 6.24 (d, J = 1.2 Hz, 1H), 5.18 (s,2H), 4.61 (s, 2H), 2.10 (s, 3H), 1.82 (s, 6H), 1.73 (s, 6H). LC- MS: m/z342.2 (M + H)⁺ 249 XI.11 VII.10

LC-MS: m/z 367.1 (M + H)⁺  270, 314 XI.12 IX.1

¹H NMR (400 MHz, DMSO- d6) δ 7.26 (d, J = 8.8 Hz, 2H), 6.72 (m, 4H),6.56 (d, J = 2.0 Hz, 2H), 4.93 (s, 2H), 2.03 (s, 3H), 1.82 (s, 6H), 1.68(s, 6H). 272 XI.13 VII.12

¹H NMR (400 MHz, DMSO- d6) δ 9.16 (s, 1H), 7.92 (dd, J₁ = 1.4 Hz, J₂ =7.8 Hz, 1H), 7.25-7.21 (m, 1H), 7.04 (d, J = 8.3 Hz, 2H), 6.91 (d, J =8.8 Hz, 1H), 6.70 (d, J = 2.0 Hz, 2H), 6.64-6.60 (m, 1H), 3.89 (s, 3H),3.62 (s, 2H).  284, 321 XI.14 Int-IX

¹H NMR (400 MHz, DMSO- d6) δ 7.40 (s, 1H), 7.23 (d, J = 8.8 Hz, 1H),6.73 (d, J = 8.3 Hz, 3H), 6.58 (d, J = 8.8 Hz, 2H), 4.97 (s, 2H), 2.03(bs, 3H), 1.82 (s, 6H), 1.71 (s, 6H).  271, 273 XI.15 VII.21

¹H NMR (400 MHz, DMSO- d6) δ 7.08 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.0Hz, 2H), 6.83 (d, J = 2.4 Hz, 1H), 6.38 (d, J = 9.2 Hz, 2H), 5.59 (s,2H), 3.00 (s, 2H), 2.02 (s, 3H), 1.78 (s, 6H), 1.70 (s, 6H). 289 311XI.16 VII.13

¹H NMR (400 MHz, DMSO- d6) δ 7.09 (d, J = 8.8 Hz, 2H), 6.81 (m, 2H),6.57-6.55 (m, 4H), 4.96 (s, 2H), 3.09 (s, 3H), 2.02 (s, 3H), 1.79 (s,6H), 1.70 (s, 6H). LC-MS: m/z 333.1 (M + H)⁺  298, 299 XI.17 VII.15

¹H NMR (400 MHz, DMSO- d6) δ 9.67 (s, 1H), 8.29 (dd, J₁ = 1.6 Hz, J₂ =4.4 Hz, 1H), 8.17 (dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H), 7.26-7.22 (m, 2H),6.73 (dd, J₁ = 4.8 Hz, J₂ = 8.0 Hz, 1H), 6.57-6.53 (m, 2H), 4.87 (s,2H), 3.87 (s, 3H). LC- MS: m/z 244.15 (M + H)⁺ 319 XI.18 VII.16

¹H NMR (400 MHz, DMSO- d6) δ 7.28 (s, 1H), 7.06 (d, J = 8.8 Hz, 2H),6.78 (d, J = 8.8 Hz, 2H), 6.72 (d, J = 8.8 Hz, 2H), 6.51 (d, J = 8.4 Hz,2H), 4.68 (s, 2H), 2.10 (bs, 1H), 1.61 (s, 2H), 1.45-1.33 (m, 8H), 1.15(s, 2H), 0.83 (s, 6H). LC-MS: m/z 347.3 (M + H)⁺ 320 XI.19 VII.17

¹H NMR (400 MHz, DMSO- d6) δ 7.46 (s, 1H), 7.07 (t, J = 7.9 Hz, 2H),6.90 (d, J = 8.8 Hz, 2H), 6.83 (m, 4H), 6.57 (m, 5H), 4.74 (s, 2H), 3.52(t, J = 7.3 Hz, 2H), 1.52 (m, 2H), 1.32 (m, 2H), 0.87 (t, J = 6.9 Hz,3H). 338 XI.20 VII.18

¹H NMR (400 MHz, DMSO- d6) δ 7.85 (s, 1H), 7.56 (d, J = 8.8 Hz, 2H),7.08 (s, 1H), 6.84 (d, J = 8.4 Hz, 2H), 6.70 (d, J = 8.0 Hz, 2H), 6.55(d, J = 8.4 Hz, 2H), 4.84 (s, 2H), 2.04 (s, 9H), 1.64 (s, 6H). LC- MS:m/z 362.3 (M + H)⁺ 339 XI.21 VIII.4

¹H NMR (400 MHz, DMSO- d6) δ 9.76 (s, 1H), 7.48 (d, J = 8.4 Hz, 2H),7.25 (d, J = 8.8 Hz, 2H), 7.87 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz,2H), 4.82 (s, 2H), 2.69 (t, J = 8.4 Hz, 2H), 2.49-2.46 (m, 2H), 2.04 (s,3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 375.3 (M + H)⁺ 345 XI.22XI.16

¹H NMR (400 MHz, DMSO- d6) δ 7.09 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.3Hz, 2H), 6.56 (t, J = 9.3 Hz, 4H), 5.27 (d, J = 7.8 Hz, 1H), 3.50-3.49(m, 1H), 3.10 (s, 3H), 2.02 (s, 3H), 1.79 (s, 6H), 1.71 (s, 6H), 1.13(d, J = 6.3 Hz, 6H).  358,  359, 376 XI.23 Int-VIII

¹H NMR (400 MHz, DMSO- d6) δ 10.06 (s, 1H), 7.66 (d, J = 8.8 Hz, 3H),7.38-7.28 (m, 3H), 7.15-7.03 (m, 3H), 6.73 (d, J = 6.8 Hz, 1H), 5.28 (s,2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). 360 XI.24 IX.2

¹H NMR (400 MHz, DMSO- d6) δ 7.41-7.38 (m, 3H), 7.21- 7.12 (m, 3H),6.84-6.78 (m, 3H), 6.63 (d, J = 8.0 Hz, 2H), 5.06 (s, 2H), 2.96-2.93 (m,1H), 1.13 (d, J = 8.0 Hz, 6H). LC-MS: m/z 338.1 (M + H)⁺ 383 XI.25 IX.3

¹H NMR (400 MHz, DMSO- d6) δ 7.39 (d, J = 2.0 Hz, 1H), 7.21 (dd, J₁ =2.4 Hz, J₂ = 8.8 Hz, 1H), 6.73-6.71 (m, 3H), 6.57 (d, J = 8.4 Hz, 2H),4.97 (s, 2H), 2.13-2.11 (m, 1H), 1.65 (s, 2H), 1.49-1.31 (m, 8H), 1.16(s, 2H), 0.84 (s, 6H). LC- MS: m/z 382.1 (M + H)⁺  366, 367 XI.26 VIII.1

¹H NMR (400 MHz, DMSO- d6) δ 9.65 (s, 1H), 7.52 (d, J = 8.4 Hz, 1H),7.43 (s, 1H), 7.35 (dd, J₁ = 1.2 Hz, J₂ = 8.0 Hz, 1H), 7.16-7.08 (m,3H), 6.75 (d, J = 7.6 Hz, 1H), 5.31 (s, 2H), 2.07 (s, 3H), 1.88 (s, 6H),1.74 (s, 6H). LC-MS: m/z 381.1 (M + H)⁺ 373 XI.27 VIII.2

¹H NMR (400 MHz, DMSO- d6) δ 10.05 (s, 1H), 7.65 (d, J = 7.6 Hz, 2H),7.32-7.27 (m, 4H), 7.09 (d, J = 7.6 Hz, 1H), 5.57 (s, 2H), 2.05 (s, 3H),1.85 (s, 6H), 1.73 (s, 6H). 395 XI.28 VIII.3

¹H NMR (400 MHz, DMSO- d6) δ 10.03 (s, 1H), 7.71-7.67 (m, 2H), 7.19-7.02(m, 7H), 6.84-6.82 (m, 4H), 5.33 (s, 2H), 3.64 (t, J = 7.2 Hz, 2H),1.60-1.54 (m, 2H), 1.34-13.2 (m, 2H), 0.88 (t, J = 7.6 Hz, 3H). LC-MS:m/z 360.2 (M + H)⁺ 378 XI.29 VII.20

LC-MS: m/z 319.2 (M + H)⁺ 348 XI.30 VII.19

LC-MS: m/z 319.5 (M + H)⁺ 266 XI.31 VII.1

LC-MS: m/z 387.15 (M + H)⁺ 521, 541, 605, 606, 607, 608, 613, 648 XI.32VII.74

LC-MS: m/z 267.1 (M + H)⁺  522, 558 XI.33 VII.75

LC-MS: m/z 281.2 (M + H)⁺. 528 XI.34 VII.76

LC-MS: m/z 325.1 (M + H)⁺. 535 XI.35 VII.77

LC-MS: m/z 233.1 (M + H)⁺. 537 XI.36 VII.78

LC-MS: m/z 350.2 (M + H)⁺. 538 XI.37 VII.79

¹H NMR (400 MHz, DMSO-d₆): δ 6.95 (d, J = 8.8 Hz, 2H), 6.8 (d, J = 8.4Hz, 2H), 6.55 (dd, J₁ = 5.2 Hz & J₂ = 8.4 Hz, 4H), 4.98 (s, 2H), 3.08(s, 3H), 2.57-2.55 (m, 1H), 2.28 (s, 1H), 2.15 (s, 1H), 1.63-1.41 (m,4H), 1.35-1.07 (m, 4H). LC-MS: m/z 293.2 (M + H)⁺. 542 XI.38 VII.80

LC-MS: m/z 267.1 (M + H)⁺. 543, 544 XI.39 IX.6

LC-MS: m/z 288.0 (M + H)⁺. 545 XI.40 VII.81

LC-MS: m/z 229.1 (M + H)⁺. 546 XI.41 IX.7

LC-MS: m/z 302.1 (M + H)⁺. 547 XI.42 VII.82

¹H NMR (400 MHz, DMSO-d₆): δ 6.80-6.73 (m, 4H), 6.63 (d, J = 8.8 Hz,2H), 6.53 (d, J = 8.4 Hz, 2H), 4.87 (s, 2H), 3.71-3.69 (m, 4H), 3.05 (s,3H), 2.95-2.92 (m, 4H). LC-MS: m/z 284.2 (M + H)⁺. 548 XI.43 VII.83

¹H NMR (400 MHz, DMSO-d₆) δ 7.08 (d, J = 8.8 Hz, 2H), 6.86- 6.83 (m,2H), 6.61-6.58 (m, 4H), 5.08 (s, 2H), 3.13 (s, 3H). LC-MS: m/z 283.1(M + H)⁺. 549 XI.44 VII.84

LC-MS: m/z 299.2 (M + H)⁺. 550 XI.45 IX.7

LC-MS: m/z 302.1 (M + H)⁺. 551 XI.46 VII.85

LC-MS: m/z 347.3 (M + H)⁺. 552 XI.47 VII.86

LC-MS: m/z 317.2 (M + H)⁺. 553 XI.48 VII.87

LC-MS: m/z 297.1 (M + H)⁺. 554 XI.49 VII.88

LC-MS: m/z 249.1 (M + H)⁺. 555 XI.50 VII.89

LC-MS: m/z 282.5 (M + H)⁺. 556 XI.51 VII.90

LC-MS: m/z 253.2 (M + H)⁺ 557 XI.52 VII.91

LC-MS: m/z 315.2 (M + H)⁺ 560, 579, 580, 614, 619, 620, 621, 625, 627,628, 629 XI.53 VII.92

LC-MS: m/z 295.2 (M + H)⁺ Also for CP compounds 630, 631, 632, 633, 634,635, 636, 637, 640, 653, 656, 657, 678, 679 561, 564 XI.54 IX.8

LC-MS: m/z 396.1 (M + H)⁺. 563 XI.55 VII.93

¹H NMR (400 MHz, DMSO-d₆): δ 7.38 (d, J = 8.8 Hz, 2H), 6.79- 6.74 (m,2H), 6.66-6.64 (m, 3H), 4.91 (s, 2H), 3.18 (s, 3H), 2.04 (s, 3H). 565XI.56 VII.94

LC-MS: m/z 311.2 (M + H)⁺. 566 XI.57 IX.9

procured 568 XI.58 VII.95

LC-MS: m/z 314.05 (M + H)⁺. 569, 570 XI.59 IX.10

LC-MS: m/z 400.2 (M + H)⁺ 571 XI.60 VII.96

LC-MS: m/z 339.1 (M + H)⁺ 572 XI.61 VII.97

LC-MS: m/z 285.1 (M + H)⁺ 573 XI.62 VII.98

¹H NMR (400 MHz, DMSO-d₆): δ 7.60-7.57 (m, 2H), 6.97-6.93 (m, 1H),6.82-6.79 (m, 1H), 6.64 (d, J = 9.2 Hz, 2H), 5.25 (s, 2H), 3.20 (s, 3H).574, 583, 584 XI.63 VII.99

LC-MS: m/z 295.2 (M + H)⁺. 575 XI.64 IX.11

LC-MS: m/z 270.1 (M + H)⁺. 576 XI.65 VII.100

LC-MS: m/z 268 (M + H)⁺ 577 XI.66 VII.101

LC-MS: m/z 307.2 (M + H)⁺ 578 XI.67 VII.102

LC-MS: m/z 282.0 (M + H)⁺ 581 XI.68 VII.103

LC-MS: m/z 282.4 (M + H)⁺ 582 XI.69 VII.104

LC-MS: m/z 296.15 (M + H)⁺ 585 XI.70 VII.105

LC-MS: m/z 311.1 (M + H)⁺ 586 XI.71 VIII.5

LC-MS: m/z 279.0 (M − H)⁻ 588 XI.72 VII.106

LC-MS: m/z 274.1 (M − H)⁻ 589 XI.73 VII.107

LC-MS: m/z 301.1 (M + H)⁺ 590 XI.74 VII.108

LC-MS: m/z 297.2 (M − H)⁻ 592 XI.75 VII.109

LC-MS: m/z 331.0 (M + H)⁺ 593 XI.76 VII.110

LC-MS: m/z 309.3 (M + H)⁺ 595 XI.77 VII.112

LC-MS: m/z 326.0 (M + H)⁺ 596 XI.78 VII.52

LC-MS: m/z 349.0 (M + H)⁺ 597 XI.79 VII.113

LC-MS: m/z 288.1 (M + H)⁺ 643, 654, 655 XI.80 VII.123

LC-MS: m/z 282.1 (M + H)⁺ 599 XI.81 IX.13

LC-MS: m/z 317.2 (M + H)⁺ 600 XI.82 IX.14

LC-MS: m/z 305.0 (M + H)⁺ 601 XI.83 IX.15

LC-MS: m/z 289.0 (M + H)⁺ 603 XI.84 VII.115

LC-MS: m/z 349.2 (M + H)⁺ 609, 652, 673, XI.85 VII.116

LC-MS: m/z 296.2 (M + H)⁺ 612 XI.86 VII.117

LC-MS: m/z 267.1 (M + H)⁺ 615 XI.87 IX.16

LC-MS: m/z 335.05 (M + H)⁺ 617 XI.88 VII.118

LC-MS: m/z 301.0 (M + H)⁺ 618 XI.89 VII.119

LC-MS: m/z 285.2 (M + H)⁺ 622 XI.90 VII.120

LC-MS: m/z 299.0 (M + H)⁺ 624 XI.91 VII.121

LC-MS: m/z 271.1 (M + H)⁺ 626 XI.92 VII.122

LC-MS: m/z 321.30 (M + H)⁺ 641 XI.93 VII.62

LC-MS: m/z 335.05 (M + H)⁺ 642 XI.94 VIII.6

LC-MS: m/z 309.1 (M + H)⁺ 646 XI.95 VII.124

LC-MS: m/z 311.2 (M + H)⁺ 647 XI.96 VII.125

LC-MS: m/z 297.1 (M + H)⁺ 659 XI.97 VII.126

LC-MS: m/z 316.2 (M + H)⁺ 660, 675, 676 XI.98  VII.63

LC-MS: m/z 369.00 (M + H)⁺ 661, 662 XI.99 VII.62

LC-MS: m/z 335.05 (M + H)⁺ 663  XI.100 VII.127

LC-MS: m/z 322.2 (M + H)⁺ 665, 666, 669, 672  XI.101 VIII.8

LC-MS: m/z 329.1 (M + H)⁺ 671, 681  XI.102 VII.128

LC-MS: m/z 329.2 (M + H)⁺ 680  XI.103 VII.69

LC-MS: m/z 315.1 (M + H)⁺ 682, 677  XI.104 VII.70

LC-MS: m/z 301.2 (M + H)⁺

Intermediate-XII

Step-a: Synthesis of methyl2-((4-((4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)amino)phenyl)amino) nicotinate (Intermediate-XII)

A solution of Intermediate-XI (8 g, 22.72 mmol, 1 eq.) and methyl2-chloronicotinate (4.27 g, 25 mmol, 1.1 eq.) in toluene (100 mL) wasde-gassed by bubbling Nitrogen gas for 5 minutes. Cesium carbonate (11.1g, 34.1 mmol, 1.5 eq.) was added followed by Palladium acetate (0.5 g,2.27 mmol, 0.1 eq.) and rac. BINAP (2.12 g, 3.41 mmol, 0.15 eq.) andde-gassed again for 5 min. Reaction mixture was heated at 110° C. understirring for 16 h. Reaction mixture was cooled to RT, diluted with ethylacetate and filtered through celite. The organic layer was adsorbed oversilica and purified by flash column chromatography. Desired product waseluted in 10% ethyl acetate in hexanes. Concentrated in vacuo to affordyellow solid (5.4 g, 49%).

¹H NMR (400 MHz, DMSO-d6) δ 9.93 (s, 1H), 8.37 (dd, J₁=2.0 Hz, J₂=4.4Hz, 1H), 8.22 (dd, J₁=2.0 Hz, J₂=7.6 Hz, 1H), 7.55 (d, J=8.8 Hz, 2H),7.41 (s, 1H), 7.31 (d, J=1.6 Hz, 1H), 7.19-7.12 (m, 2H), 7.04 (d, J=8.8Hz, 2H), 6.84-6.81 (m, 1H), 3.89 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H),1.72 (s, 6H); LC-MS: m/z 488.1 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-XII using appropriate reactants and reagents employingsuitable Pd catalysts and ligands and in presence of suitable solventsand appropriate reaction conditions.

Inter- mediate Reac- CP No. tant Structure Analytical data 57  XII.1 VII.1

¹H NMR (500 MHz, CDCl₃) δ 9.45 (s, 1H), 8.01 (s, 1H), 7.45-7.23. (d,2H), 7.23-7.01 (m, 6H), 6.98-7.01 (d, 2H), 6.94 (s, 1H), 3.93 (s, 3H),5.99 (s, 1H) 2.21-1.98 (m, 15H) LC-MS: m/z 521.2 (M + H)⁺ 59  XII.2 XI.31

¹H NMR (500 MHz, DMSO-d6) δ 9.45 (s, 1H), 8.01 (s, 1H), 7.49-7.33. (d,2H), 7.23-7.01 (m, 5H), 6.91-7.04 (d, 2H), 6.94 (s, 1H), 3.93 (s, 3H),5.99 (s, 1H) 2.21-1.98 (m, 15H) LC-MS: m/z 522.2 (M + H)⁺ 60  XII.3 XI.31

LC-MS: m/z 535.6 (M + H)⁺ 61  XII.4  XI.31

LC-MS: m/z 589.2 (M + H)⁺ 62  XII.5 

LC-MS: m/z 539.5 (M + H)⁺ 65  XII.6 

LC-MS: m/z 468.3 (M + H)⁺ 66  XII.7  XI.1

LC-MS: m/z 556 (M + H)⁺ 67  XII.8  XI.3

LC-MS: m/z 489 (M + H)⁺ 146 XII.9  I.13

¹H NMR (400 MHz, DMSO-d6) δ 9.29 (s, 1H), 7.89 (dd, J₁ = 1.6 Hz, J₂ =8.0 Hz, 1H), 7.49-742 (m, 5H), 7.33-7.25 (m, 5H), 7.15-7.13 (m, 3H),6.94-6.86 (m, 1H), 3.83 (s, 3H). LC-MS: m/z 370.1 (M + H)⁺ 156 XII.10 Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 9.05 (s, 1H), 7.93 (dd, J₁ = 1.2 Hz, J₂ =3.6 Hz, 1H), 7.59 (s, 1H), 7.42- 7.34 (m, 3H), 7.21 (s, 2H), 7.13 (d, J= 8.8 Hz, 1H), 7.05 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.04 (s, 3H),1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.1 (M + H)⁺ 157 XII.11  Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 8.77 (s, 1H), 8.38 (s, 1H), 7.95 (d, J = 5.6Hz, 1H), 7.63 (d, J = 4.8 Hz, 1H), 7.60 (s, 1H), 7.34 (s, 1H), 7.22 (s,2H), 7.18 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H),2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.1 (M + H)⁺ 159XII.12  Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.88 (s, 1H), 8.69 (s, 1H),7.58 (s, 1H), 7.50 (d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.21 (s, 2H), 7.04(d, J = 8.8 Hz, 2H), 4.38 (q, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s,6H), 1.36 (t, J = 7.2 Hz, 3H). LC-MS: m/z 503.2 (M + H)⁺ 160 XII.13 Int-XI

LC-MS: m/z 489.1 (M + H)⁺ 163 XII.14  Int-XI

LC-MS: m/z 502.1 (M + H)⁺ 168 XII.15  Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.66(d, J = 8.0 Hz, 1H), 7.37 (d, J = 7.2 Hz, 1H), 7.29 (d, J = 2.0 Hz, 1H),7.26 (s, 1H), 7.14 (dd, J₁ = 2.0 Hz, J₂ = 8.8 Hz, 1H), 7.04 (t, J = 8.8Hz, 3H), 6.98 (d, J = 8.4 Hz, 1H), 4.31 (q, 2H), 2.04 (s, 3H), 1.82 (s,6H), 1.72 (s, 6H), 1.33 (t, J = 6.8 Hz, 3H). LC-MS: m/z 502.2 (M + H)⁺169 XII.16  XI.3

¹H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H), 8.35-8.32 (m, 2H), 8.22 (dd,J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H), 8.17 (s, 1H), 7.91 (d, J = 8.8 Hz, 1H),7.85 (dd, J₁ = 2.8 Hz, J₂ = 9.2 Hz, 1H), 7.34 (d, J = 2.4 Hz, 1H), 7.27(dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 1H), 6.98 (d, J = 8.8 Hz, 1H), 6.84 (dd,J₁ = 4.4 Hz, J₂ = 8.0 Hz, 1H), 3.90 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H),1.74 (s, 6H). LC-MS: m/z 489.1 (M + H)⁺ 191 XII.17  XI.4

¹H NMR (400 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.60 (m, 1H), 8.40 (m, 1H),7.97 (s, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.13 (m, 1H), 7.03 (m, 3H), 6.81(m, 3H), 3.92 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS:m/z 454.1 (M + H)⁺ 202 236 XII.18  XI.8

¹H NMR (400 MHz, DMSO-d6) δ 9.78 (s, 1H), 8.40 (dd, J₁ = 2.0 Hz, J₂ =5.2 Hz, 1H), 8.21 (s, 1H), 8.19- 8.18 (m, 1H), 7.72 (s, 1H), 7.31 (d, J= 1.6 Hz, 1H), 7.29 (d, J = 2.0 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 6.80(dd, J₁ = 4.4 Hz, J₂ = 7.2 Hz, 1H), 5.37 (s, 2H), 3.88 (s, 3H), 2.04 (s,3H), 1.83 (s, 6H), 1.72 (s, 6H). LC- MS: m/z 477.2 (M + H)⁺ 203 XII.19 XI.5

¹H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 1H), 8.36 (dd, J₁ = 2.0 Hz, J₂ =4.9 Hz, 1H), 8.24 (dd, J₁ = 2.0 Hz, J₂ = 7.8 Hz, 1H), 7.62 (d, J == 1.0Hz, 1H), 7.36 (s, 1H), 7.30 (d, J = 7.3 Hz, 1H), 7.24-7.11 (m, 4H),6.88-6.85 (m, 1H), 6.78 (d, J = 7.8 Hz, 1H), 4.06 (s, 2H), 3.88 (s, 3H),3.17 (m, 1H), 1.15 (d, J = 6.8 Hz, 6H). LC-MS: m/z 361.2 (M + H)⁺ 204XII.20  XI.7

¹H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 1H), 8.39 (dd, J₁ = 2.0 Hz, J₂ =4.8 Hz, 1H), 8.25 (dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H), 7.57 (s, 1H), 7.48(s, 1H), 7.36-7.31 (m, 2H), 7.24 (dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz, 1H),7.15 (d, J = 6.0 Hz, 2H), 6.88 (dd, J₁ = 4.8 Hz, J₂ = 7.6 Hz, 1H),6.70-6.68 (m, 1H), 3.89 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s,6H). LC-MS: m/z 488.3 (M + H)⁺ 205 XII.21  Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 9.68 (s, 1H), 8.43 (s, 1H), 8.35 (s, 1H),7.68 (d, J = 8.8 Hz, 2H), 7.38 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.16(d, J = 2.0 Hz, 1H), 7.12 (d, J = 8.8 Hz, 1H), 7.06 (d, J = 8.8 Hz, 2H),3.89 (s, 3H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC- MS: m/z489.3 (M + H)⁺ 206 XII.22  Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 8.43 (dd, J₁ = 2.9 Hz, J₂ = 4.4 Hz, 2H),8.38 (s, 1H), 7.71 (t, J = 2.9 Hz, 1H), 7.20-7.17 (m, 2H), 7.06-7.04 (m,4H), 3.85 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). 207 XII.23 Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.21 (d, J = 5.4 Hz, 1H), 7.54(s, 1H), 7.45 (d, J = 2.4 Hz, 1H), 7.34 (s, 1H), 7.20 (s, 2H), 7.11-7.04 (m, 4H), 6.93- 6.91 (m, 1H), 3.82 (s, 3H), 2.04 (s, 3H), 1.83 (s,6H), 1.72 (s, 6H).  211, 268 XII.24  XI.1

LC-MS: m/z 570.2 (M + H)⁺ 226 XII.25  XI.9

LC-MS: m/z 478.2 (M + H)⁺ 228 XII.26  XI.6

¹H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.33 (dd, J₁ = 2.0 Hz, J₂ =5.2 Hz, 1H), 8.21 (dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H), 7.42- 7.40 (m,2H), 7.33 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H), 7.00-6.92 (m, 3H), 6.82(dd, J₁ = 4.8 Hz, J₂ = 7.6 Hz, 1H), 4.31 (s, 2H), 3.88 (s, 3H), 3.37 (t,J = 8.0 Hz, 2H), 2.89 (t, J = 8.2 Hz, 2H), 2.05 (s, 3H), 1.85 (d, J =2.4 Hz, 6H), 1.73 (s, 6H). LC-MS: m/z 528.2 (M + H)⁺ 240 XII.27  XI.10

LC-MS: m/z 477.2 (M + H)⁺ 249 XII.28  XI.11

¹H NMR (400 MHz, DMSO-d6) δ 9.79 (s, 1H), 8.31 (dd, J₁ = 2.0 Hz, J₂ =4.8 Hz, 1H), 8.19 (dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H), 7.48 (d, J = 2.0Hz, 1H), 7.43-7.39 (m, 3H), 7.29 (d, J = 8.0 Hz, 1H), 6.77 (dd, J₁ = 4.4Hz, J₂ = 8.4 Hz, 1H), 6.52 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.18 (s,3H), 2.07 (s, 3H), 1.89 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 502.1 (M + H)⁺261 XII.29  XI.7

¹H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 7.69 (t, J = 8.0 Hz, 1H),7.43-7.38 (m, 4H), 7.32 (dd, J₁ = 2.0 Hz, J₂ = 10.8 Hz, 2H), 7.20 (dd,J₁ = 2.0 Hz, J₂ = 8.4 Hz, 1H), 7.13 (t, J = 8.0 J = 8.0 Hz, 1H), 6.63(t, J = 8.4 Hz, 1H), 4.28-4.23 (q, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72(s, 6H), 1.26 (t, J = 7.2 Hz, 3H). LC-MS: m/z 500.1 (M − H)⁻ 262 XII.30 Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 7.56 (t, J = 8.0 Hz, 1H), 7.47(d, J = 8.8 Hz, 2H), 7.28- 7.23 (m, 2H), 7.13 (dd, J₁ = 2.0 Hz, J₂ = 8.8Hz, 1H), 7.11-6.93 (m, 4H), 6.66 (d, J = 8.4 Hz, 1H), 6.58 (d, J = 7.2Hz, 1H), 2.04 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H), 1.42 (s, 18H). LC-MS: m/z 645.1 (M + H)⁺ 263 XII.31  XI.1

¹H NMR (400 MHz, DMSO-d6) δ 11.68 (s, 1H), 9.11 (s, 1H), 8.53 (d, J =1.6 Hz, 1H), 8.29 (d, J = 2.4 Hz, 1H), 7.61 (s, 1H), 7.55 (s, 1H), 7.51-7.46 (m, 2H), 7.36 (s, 1H), 7.23 (s, 1H), 3.78 (s, 3H), 1.97 (s, 3H),1.72-1.61 (m, 13H). LC-MS: m/z 520.2 (M + H)⁺ 267 XII.32  XI.1

¹H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.56 (dd, J₁ = 1.6 Hz, J₂ =6.4 Hz, 2H), 8.12 (s, 1H), 7.91 (d, J = 2.4 Hz, 1H), 7.41 (d, J = 2.0Hz, 1H), 7.36-7.28 (m, 2H), 6.84 (s, 1H), 6.74 (d, J = 15.6 Hz, 2H),3.89 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 556.0(M + H)⁺ 271 XII.33  XI.15

¹H NMR (400 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.47 (dd, J₁ = 2.0 Hz, J₂ =4.8 Hz, 1H), 8.33-8.30 (m, 2H), 7.96 (dd, J₁ = 2.4 Hz, J₂ = 8.4 Hz, 1H),7.30 (d, J = 8.4 Hz, 1H), 7.13 (d, J = 8.8 Hz, 2H), 6.98 (dd, J₁ = 4.4Hz, J₂ = 7.6 Hz, 1H), 6.45 (d, J = 8.8 Hz, 2H), 3.93 (s, 3H), 3.09 (s,3H), 2.02 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 536.1 (M + H)⁺273 XII.34  XI.15

¹H NMR (400 MHz, DMSO-d6) δ 9.31 (s, 1H), 7.92 (dd, J₁ = 1.2 Hz, J₂ =7.6 Hz, 1H), 7.77-7.74 (m, 1H), 7.61 (d, J = 2.4 Hz, 1H), 7.56 (dd, J₁ =2.4 Hz, J₂ = 8.8 Hz, 1H), 7.52-7.46 (m, 2H), 7.36 (d, J = 8.4 Hz, 1H),7.26 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.8 Hz, 1H), 6.94 (t, J = 7.6 Hz,1H), 6.47 (d, J = 9.2 Hz, 1H), 3.86 (s, 3H), 3.31 (s, 3H), 2.02 (s, 3H),1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 535.1 (M + H)⁺ 275 XII.35  XI.3

¹H NMR (400 MHz, CDCl3) δ 9.19 (s, 1H), 8.11 (d, J = 2.4 Hz, 1H), 7.95(dd, J₁ = 1.6 Hz, J₂ = 8.4 Hz, 1H), 7.41 (dd, J₁ = 2.8 Hz, J₂ = 8.8 Hz,1H), 7.34 (d, J = 8.8 Hz, 2H), 7.30-7.26 (m, 3H), 6.92-6.86 (m, 2H),6.69 (t, J = 8.0 Hz, 1H), 6.63 (s, 1H), 3.91 (s, 3H), 2.10 (s, 3H), 1.91(s, 6H), 1.81-1.73 (m, 6H). LC-MS: m/z 454.1 (M + H)⁺ 284 XII.36  XI.14

¹H NMR (400 MHz, DMSO-d6) δ 9.23 (s, 1H), 7.89 (d, J = 1.9 Hz, 1H), 7.76(m, 1H), 7.49 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.10 (m, 2H), 6.97 (d,J = 8.8 Hz, 2H), 6.77 (m, 1H), 3.86 (s, 3H), 2.05 (s, 3H), 1.81 (s, 6H),1.70 (s, 6H). 289 XII.37  XI.16

¹H NMR (400 MHz, DMSO-d6) δ 7.67- 7.59 (m, 2H), 7.34- 7.27 (m, 2H), 7.12(d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 6.65 (d, J = 8.4 Hz, 2H),6.55 (d, J = 8.8 Hz, 2H), 4.01-3.95 (m, 2H), 3.71-3.66 (m, 2H), 3.12 (s,3H), 2.03 (s, 3H), 1.84 (s, 6H), 1.68 (s, 6H), 1.16 (t, J = 6.8 Hz, 3H),1.07 (t, J = 7.6 Hz, 3H). LC-MS: m/z 509.1 (M + H)⁺ 290 XII.38  XI.16

¹H NMR (400 MHz, DMSO-d6) δ 9.23 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H),7.75-7.73 (m, 1H), 7.52-7.46 (m, 1H), 7.42-7.36 (m, 1H), 7.26 (d, J =8.8 Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 7.06 (d, J = 8.4 Hz, 1H),6.99-6.95 (m, 2H), 6.75-6.71 (m, 1H), 4.33-4.31 (m, 2H), 3.23 (s, 3H),2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H), 1.34 (t, J = 6.9 Hz, 3H).LC-MS: m/z 481.0 (M + H)⁺ 311 XII.39  XI.16

LC-MS: m/z 482.1 (M + H)⁺ 314 XII.40  XI.12

¹H NMR (400 MHz, DMSO-d6) δ 10.02 (s, 1H), 8.39 (dd, J₁ = 1.9 Hz, J₂ =4.9 Hz, 1H), 6.25 (dd, J₁ = 1.9 Hz, J₂ = 7.8 Hz, 1H), 7.70 (d, J = 8.8Hz, 2H), 7.34 (d, J = 8.9 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 6.89- 6.88(m, 3H), 3.90 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). 319XII.41  XI.18

¹H NMR (400 MHz, DMSO-d6) δ 9.07 (s, 1H), 7.78 (s, 1H), 7.66-7.62 (m,3H), 7.34 (d, J = 7.6 Hz, 1H), 7.16 (d, J = 8.8 Hz, 2H), 7.01-6.92 (m,5H), 4.33-4.28 (m, 2H), 2.12 (s, 1H), 1.65 (s, 2H), 1.49- 1.31 (m, 11H),1.17 (s, 2H), 0.85 (s, 6H). LC-MS: m/z 496.3 (M + H)⁺ 320 XII.42  XI.19

¹H NMR (400 MHz, DMSO-d6) δ 9.12 (s, 1H), 7.91 (s, 1H), 7.65 (m, 3H),7.36 (d, J = 6.9 Hz, 1H), 7.11 (t, J = 7.8 Hz, 2H), 7.02 (m, 7H), 6.65(m, 3H), 4.32 (m, 2H), 3.56 (t, J = 7.3 Hz, 2H), 1.50 (m, 2H), 1.30 (m,5H), 0.88 (t, J = 7.3 Hz, 3H). 321 XII.43  XI.14

¹H NMR (400 MHz, DMSO-d6) δ 9.34 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.70(t, J = 7.4 Hz, 1H),7.47 (d, J = 2.4 Hz, 1H), 7.42 (d, J = 7.4 Hz, 1H),7.30 (dd, J₁ = 2.5 Hz, J₂ = 8.8 Hz, 1H), 7.03 (d, J = 8.8 Hz, 1H), 6.92(m, 3H), 4.32 (m, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.72 (s, 6H), 1.33(t, J = 6.8 Hz, 3H). 322 XII.44  XI.16

¹H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 2.4 Hz, 1H), 8.15 (dd, J₁ = 2.4Hz, J₂ = 8.8 Hz, 2H), 7.36 (d, J = 8.8 Hz, 2H), 7.15- 7.12 (m, 4H), 7.05(d, J = 9.2 Hz, 2H), 6.91 (t, J = 6.0 Hz, 3H), 3.85 (s, 6H), 3.28 (s,3H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 603.3 (M + H)⁺338 XII.45  XI.20

¹H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.27 (s, 1H), 7.75 (d, J = 8.8Hz, 2H), 7.70-7.63 (m, 3H), 7.38 (t, J = 7.6 Hz, 1H), 7.18 (s, 1H), 7.08(d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.0 Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H),4.34- 4.29 (m, 2H), 2.05 (s, 9H), 1.65 (s, 6H), 1.34 (t, J = 7.2 Hz,3H). LC-MS: m/z 511.3 (M + H)⁺ 339 XII.46  XI.21

¹H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 9.25 (s, 1H), 7.88 (d, J = 7.2Hz, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.37 (t, J = 8.8 Hz, 1H), ¹H NMR (400MHz, DMSO-d6) δ 7.27- 7.23 (m, 4H), 7.17- 7.12 (m, 3H), 6.76 (t, J = 7.6Hz, 1H), 3.84 (s, 3H), 3.30 (t, J = 7.2 Hz, 2H), 2.60 (t, J = 7.6 Hz,2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 509.3 (M + H)⁺345 XII.47  XI.22

LC-MS: m/z 509.4 (M + H)⁺ 352 XII.48  XI.30

¹H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.26 (s, 1H), 8.12 (d, J = 6.8Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.60-7.41 (m, 2H), 7.29-7.21 (m, 4H),7.08 (t, J = 8.8 Hz, 5H), 2.08 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H).LC-MS: m/z 423.3 (M + H)⁺ 358 XII.49  XI.28

¹H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 10.19 (s, 1H), 8.45 (dd, J₁ =2.0 Hz, J₂ = 4.8 Hz, 1H), 8.29 (dd, J₁ = 2.0 Hz, J₂ = 7.6 Hz, 1H), 8.17(s, 1H), 8.03 (dd, J₁ = 1.2 Hz, J₂ = 8.0 Hz, 1H), 7.70 (d, J = 8.8 Hz,2H), 7.60 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 8.0 Hz, 1H), 7.33 (d, J =8.8 Hz, 2H), 6.94 (dd, J₁ = 4.8 Hz, J₂ = 8.0 Hz, 1H), 3.92 (s, 3H), 2.06(s, 3H), 1.86 (d, J = 2.4 Hz, 6H), 1.74 (s, 6H). LC-MS: m/z 482.3 (M +H)⁺ 359 XII.50  XI.28

¹H NMR (400 MHz, DMSO-d6) δ 10.14 (s, 1H), 8.65 (s, 1H), 7.69-7.67 (m,3H), 7.61 (s, 1H), 7.45- 7.38 (m, 5H), 7.33- 7.31 (m, 3H), 3.83 (s, 3H),2.05 (s, 3H), 1.85 (d, J = 2.8 Hz, 6H), 1.73 (s, 6H). LC- MS: m/z 481.2(M + H)⁺ 360 XII.51  XI.24

¹H NMR (400 MHz, DMSO-d6) δ 9.26 (s, 1H), 7.90 (d, J = 7.9 Hz, 1H), 7.45(m, 4H), 7.37-7.07 (m, 9H), 6.79 (t, J = 7.8 Hz, 1H), 3.86 (s, 3H), 2.97(m, 1H), 1.20 (d, J = 6.9 Hz, 6H). 362 XII.52  XI.16

¹H NMR (400 MHz, DMSO-d6) δ 7.57 (s, 1H), 7.24-7.19 (m, 3H), 7.01 (d, J= 8.8 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.3 Hz, 2H), 6.68(d, J = 8.3 Hz, 1H), 6.53 (d, J = 8.3 Hz, 1H), 3.75 (s, 6H), 3.19 (s,3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). 366 XII.53  XI.26

¹H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 9.96 (s, 1H), 8.45 (dd, J₁ =2.0 Hz, J₂ = 4.8 Hz, 1H), 8.30 (dd, J₁ = 2.0 Hz, J₂ = 7.6 Hz, 1H), 8.23(s, H), 8.07-8.04 (m, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.55-7.46 (m, 3H),7.38 (dd, J₁ = 2.4 Hz, J₂ = 8.0 Hz, 1H), 6.95 (dd, J₁ = 4.8 Hz, J₂ = 7.6Hz, 1H), 3.92 (s, 3H), 2.08 (s, 3H), 1.89 (s, 6H), 1.75 (s, 6H). LC-MS:m/z 516.2 (M + H)⁺ 367 XII.54  XI.26

¹H NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1H), 9.42 (s, 1H), 7.93 (dd, J₁ =1.6 Hz, J₂ = 8.0 Hz, 1H), 7.83 (s, 1H), 7.70-7.60 (m, 1H), 7.51-7.34 (m,5H), 7.40-7.30 (m, 2H), 6.90-6.86 (m, 1H), 3.87 (s, 3H), 2.07 (s, 3H),1.88 (d, J = 2.4 Hz, 6H), 1.74 (s, 6H). LC-MS: m/z 515.3 (M + H)⁺ 373XII.55  XI.27

¹H NMR (400 MHz, DMSO-d6) δ 10.63 (s, 1H), 10.23 (s, 1H), 9.15 (d, J =1.6 Hz, 1H), 8.50 (dd, J₁ = 2.0 Hz, J₂ = 4.8 Hz, 1H), 8.35 (dd, J₁ = 2.0Hz, J₂ = 7.6 Hz, 1H), 7.70- 7.67 (m, 3H), 7.63- 7.61 (m, 1H), 7.33 (d, J= 8.8 Hz, 2H), 7.02 (dd, J₁ = 4.4 Hz, J₂ = 7.6 Hz, 1H), 3.94 (s, 3H),2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC- MS: m/z 516.2 (M + H)⁺ 375352 XII.56  XII.48

¹H NMR (400 MHz, DMSO-d6) δ 7.71 (s, 1H), 7.16-6.77 (m, 13H), 4.07-4.00(m, 2H), 2.87 (t, J = 7.6 Hz, 2H), 2.59 (d, J = 8.0 Hz, 2H), 2.04 (s,3H), 1.81 (s, 6H), 1.69 (s, 6H), 1.15 (t, J = 4.0 Hz, 3H), LC- MS: m/z495.3 (M + H)⁺ 376 XII.57  XI.28

¹H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H), 7.87 (s, 1H), 7.67 (d, J =8.8 Hz, 2H), 7.54 (s, 1H), 7.38 (d, J = 18.4 Hz, 1H), 7.34-7.28 (m, 4H),7.20-7.10 (m, 1H), 7.85 (d, J = 8.0 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H),3.78 (s, 3H), 3.72 (s, 3H), 2.06 (s, 3H), 1.86 (d, J = 2.4 Hz, 6H), 1.74(s, 6H). LC-MS: m/z 511.2 (M + H)⁺ 377 XII.58  XI.30

¹H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H), 7.93 (s, 1H), 7.20 (d, J = 8.8Hz, 2H), 7.03-6.97 (m, 6H), 6.06 (d, J = 2.0 Hz, 1H), 6.00 (d, J = 2.0Hz, 1H), 3.74 (s, 3H), 3.73 (s, 3H), 3.67 (s, 3H), 2.04 (s, 3H), 1.82(s, 6H), 1.72 (s, 6H). LC-MS: m/z 513.3 (M + H)⁺ 379 XII.59  XI.16

¹H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 7.36 (d, J = 2.4 Hz, 1H), 7.24(d, J = 8.8 Hz, 2H), 7.10 (dd, J₁ = 2.0 Hz, J₂ = 5.2 Hz, 4H), 6.97 (d, J= 8.4 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H), 3.72 (s, 3H),3.21 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.76 (s, 6H). LC- MS: m/z497.3 (M + H)⁺ 380 XII.60  XI.30

¹H NMR (400 MHz, DMSO-d6) δ 9.29 (s, 1H), 8.03 (s, 1H), 7.82 (d, J = 8.8Hz, 1H), 7.22 (d, J = 6.0 Hz, 2H), 7.13 (d, J = 8.8 Hz, 2H), 7.07 (d, J= 8.8 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 6.41 (d, J = 2.4 Hz, 1H), 6.32(dd, J₁ = 2.4 Hz, J₂ = 9.2 Hz, 1H), 3.81 (s, 3H), 3.69 (s, 3H), 2.05 (s,3H), 1.83 (d, J = 2.8 Hz, 6H), 1.73 (s, 6H). LC-MS: m/z 483.3 (M + H)⁺382 XII.61  XI.14

¹H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 8.38 (dd, J₁ = 2.0 Hz, J₂ =4.9 Hz, 1H), 8.25 (dd, J₁ = 1.9 Hz, J₂ = 7.8 Hz, 1H), 7.69 (dd, J₁ = 2.0Hz, J₂ = 6.8 Hz, 2H), 7.49 (d, J = 2.5 Hz, 1H), 7.32 (dd, J₁ = 2.4 Hz,J₂ = 8.8 Hz, 1H), 6.98 (d, J = 8.3 Hz, 1H), 6.95 (dd, J₁ = 1.9 Hz, J₂ =6.8 Hz, 2H), 6.87 (dd, J₁ = 4.4 Hz, J₂ = 7.3 Hz, 1H), 3.90 (s, 3H), 2.06(s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 489.1 (M + H)⁺ 383XII.62  XI.25

¹H NMR (400 MHz, DMSO-d6) δ 9.24 (s, 1H), 7.88 (dd, J₁ = 1.6 Hz, J₂ =8.0 Hz, 1H), 7.50 (d, J = 2.4 Hz, 1H), 7.39-7.32 (m, 2H), 7.26 (d, J =8.8 Hz, 2H), 7.10-7.03 (m, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.77 (t, J =8.0 Hz, 1H), 3.85 (s, 3H), 2.16- 2.12 (m, 1H), 1.69 (s, 2H), 1.53-1.35(m, 8H), 1.18 (s, 2H), 0.86 (s, 6H). 384 XII.63  XI.25

¹H NMR (400 MHz, DMSO-d6) δ 10.02 (s, 1H), 8.38 (dd, J₁ = 2.0 Hz, J₂ =4.8 Hz, 1H), 8.25 (dd, J₁ = 2.0 Hz, J₂ = 7.6 Hz, 1H), 7.70-7.67 (m, 2H),7.48 (d, J = 2.4 Hz, 1H), 7.33-7.30 (m, 1H), 6.98-6.93 (m, 3H),6.89-6.86 (m, 1H), 3.90 (s, 3H), 2.14-2.13 (m, 1H), 1.69-1.68 (m, 2H),1.52-1.35 (m, 8H), 1.18 (s, 2H), 0.86 (s, 6H). 395 XII.64  XI.28

¹H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H), 9.41 (s, 1H), 7.92 (dd, J₁ =1.2 Hz, J₂ = 7.6 Hz, 1H), 7.8 (s, 1H), 7.69 (d, J = 9.2 Hz, 2H), 7.64(d, J = 7.6 Hz, 1H), 7.52- 7.44 (m, 3H), 7.31 (d, J = 8.4 Hz, 1H), 7.22-7.18 (m, 2H), 7.03 (d, J = 8.8 Hz, 2H), 6.89- 6.79 (m, 4H), 3.87 (s,3H), 3.65 (t, J = 7.6 Hz, 2H), 1.58-1.51 (m, 2H), 1.38-1.30 (m, 2H),0.88 (t, J = 7.6 Hz, 3H). LC- MS: m/z 494.3 (M + H)⁺ 398 XII.65  XI.28

¹H NMR (400 MHz, DMSO-d6) δ 10.21- 10.17 (m, 2H), 8.44 (d, J = 2.8 Hz,1H), 8.27 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H), 8.15 (s, 1H), 8.01 (d, J =8.4 Hz, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.59 (d, J = 8.0 Hz, 1H), 7.46(t, J = 8.0 Hz, 1H), 7.19 (t, J = 8.4 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H),6.92 (dd, J₁ = 4.8 Hz, J₂ = 8.0 Hz, 1H), 6.85-6.77 (m, 3H), 3.91 (s,3H), 3.64 (t, J = 7.2 Hz, 2H), 1.55-1.52 (m, 2H), 1.35-1.29 (m, 2H),0.87 (t, J = 4.8 Hz, 3H). LC-MS: m/z 495.3 (M + H)⁺ 420 XII.66  XI.16

¹H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 7.37 (s, 1H), 7.24 (d, J = 8.8Hz, 2H), 7.12-7.10 (m, 4H), 6.95 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.4Hz, 2H), 4.04 (t, J = 4.4 Hz, 2H), 3.85 (s, 3H), 3.63 (t, J = 4.8 Hz,2H), 3.30 (s, 3H), 3.21 (s, 3H), 2.04 (s, 3H), 1.83 (d, J = 2.4 Hz, 6H),1.72 (s, 6H). LC-MS: m/z 541.2 (M + H)⁺ 270 XII.67  XI.12

LC-MS: m/z 454.1 (M + H)⁺ 266 XII.68  XI.31

LC-MS: m/z 522.1 (M + H)⁺ 231 XII.69  Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.52-8.47 (m, 2H), 7.55 (s,1H), 7.47 (d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.20 (s, 2H), 7.03 (d, J =8.8 Hz, 2H), 6.94- 6.91 (m, 1H), 2.05 (s, 3H), 1.84 (s, 6H), 1.72 (s,6H). LC-MS: m/z 475.2 (M + H)⁺ 453 XII.70  XI.16

¹H NMR (400 MHz, DMSO-d6): δ 8.79 (s, 1H), 7.54-7.52 (m, 1H), 7.44-7.42(m, 1H), 7.28-6.98 (m, 9H), 3.85 (s, 3H), 3.80 (d, J = 2.4 Hz, 2H), 3.37(s, 3H), 2.04 (s, 3H), 2.00- 1.96 (m, 1H), 1.83 (s, 6H), 1.72 (s, 6H),0.97 (d, J = 6.4 Hz, 6H). 521 XII.71  XI.32

LC-MS: m/z 431.2 (M + H)+ 522 XII.72  XI.33

LC-MS: m/z 445.2 525 XII.73  VII.78

LC-MS: m/z 580.4 (M + H)+ 526 XII.74  XI.16

LC-MS: m/z 554.4 (M + H)+ 528 XII.75  XI.34

LC-MS: m/z 489.1 (M + H)+ 535 XII.76  XI.35

LC-MS: m/z 396.1 (M + H)+ 536 XII.77  VII.81

LC-MS: m/z 488.3 (M + H)+ 537 XII.78  XI.36

LC-MS: m/z 514.3 (M + H)+ 538 XII.79  XI.37

LC-MS: m/z 456.3 (M + H)+ 541 XII.80  VII.80

LC-MS: m/z 402.1 (M + H)+. 542 XII.81  XI.38

LC-MS: m/z 431.31 (M + H)+ 543 XII.82  XI.39

LC-MS: m/z 422.1 (M + H)+ 544 XII.83  XI.39

LC-MS: m/z 452.1 (M + H)+ 545 XII.84  XI.40

LC-MS: m/z 392.2 (M + H)+ 546 XII.85  XI.41

LC-MS: m/z 436.2 547 XII.86  XI.42

LC-MS: m/z 448.2 (M + H)+. 548 XII.87  XI.43

LC-MS: m/z 447.1 (M + H)+. 549 XII.88  XI.44

LC-MS: m/z 463.2 (M + H)+. 550 XII.89  XI.45

LC-MS: m/z 466.2 (M + H)+ 551 XII.90  XI.46

LC-MS: m/z 511.4 (M + H)+ 552 XII.91  XI.47

LC-MS: m/z 481.2 (M + H)+ 553 XII.92  XI.48

LC-MS: m/z 461.1 (M + H)+. 554 XII.93  XI.49

LC-MS: m/z 391.3 (M + H)+ 555 XII.94  XI.50

LC-MS: m/z 446.3 (M + H)+. 556 XII.95  XI.51

LC-MS: m/z 417.2 (M + H)+ 557 XII.96  XI.52

LC-MS: m/z 479.2 (M + H)+ 558 XII.97  XI.33

LC-MS: m/z 416.2 (M + H)+ 559 XII.98  XI.31

LC-MS: m/z 538.2 (M + H)+ 560 XII.99  XI.53

LC-MS: m/z 459.3 (M + H)+ 561 XII.100 XI.54

Proceeded with crude/TLC reference 563 XII.101 XI.55

LC-MS: m/z 444.1 (M + H)+ 564 XII.102 XI.54

LC-MS: m/z 515.15 (M + H)+. 565 XII.103 XI.56

LC-MS: m/z 475.1 (M + H)+. 566 XII.104 XI.57

LC-MS: m/z 437.2 (M + H)+ 567 XII.105 VII.88

LC-MS: m/z 391.3 (M + H)+ 568 XII.106 XI.58

LC-MS: m/z 479.2 (M + H)+ 570 XII.107 XI.59

LC-MS: m/z 449.3 (M + H)+ 571 XII.108 XI.60

LC-MS: m/z 503.2 (M + H)+ 572 XII.109 XI.61

LC-MS: m/z 449.3 (M + H)+ 573 XII.110 XI.62

LC-MS: m/z 507.1 (M + H)+ 574 XII.111 XI.63

LC-MS: m/z 459.3 (M + H)+ 575 XII.112 XI.64

LC-MS: m/z 434.1 (M + H)+ 576 XII.113 XI.65

LC-MS: m/z 431.55 (M + H)+ 577 XII.114 XI.66

LC-MS: m/z 469.25 (M − H)+ 578 XII.115 XI.67

LC-MS: m/z 446.05 (M + H)+ 579 XII.116 XI.53

LC-MS: m/z 496.05 (M + H)+ 580 XII.117 XI.53

LC-MS: m/z 512.10 (M + H)+. 581 XII.118 XI.68

LC-MS: m/z 446.65 (M + H)⁺ 582 XII.119 XI.69

1H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 7.35 (d, J = 2.8 Hz, 1H),7.15-7.10 (m, 6H), 7.00-6.98 (m, 2H), 6.90-6.87 (m, 2H 3.85 (s, 3H),3.72 (s, 3H), 3.24- 3.21 (m, 5H), 2.67- 2.58 (m, 6H), 1.85- 1.74 (m, 4H)LC-MS: m/z 459.25 (M + H)+ 585 XII.120 XI.70

LC-MS: m/z 475.3 (M + H)+ 586 XII.121 XI.71

LC-MS: m/z 445.0 (M + H)+ 587 XII.122 IX.12

LC-MS: m/z 418.2 (M + H)+ 588 XII.123 XI.72

LC-MS: m/z 438.1 (M + H)+ 589 XII.124 XI.73

LC-MS: m/z 465.2 (M + H)+ 590 XII.125 XI.74

LC-MS: m/z 461.2 (M + H)+ 591 XII.126 IX.9

LC-MS: m/z 467.05 (M + H)+ 592 XII.127 XI.75

LC-MS: m/z 432.2 (M + H)+ 593 XII.128 XI.76

LC-MS: m/z 472.1 (M + H)+ 594 XII.129 VII.111

LC-MS: m/z 447.1 (M + H)+ 595 XII.130 XI.77

LC-MS: m/z 490.1 (M + H)+ 596 XII.131 XI.78

LC-MS: m/z 448.2 (M + H)+ 597 XII.132 XI.79

LC-MS: m/z 452.2 (M + H)+ 598 XII.133 VII.123

LC-MS: m/z 446.05 (M + H)+ 599 XII.134 XI.81

LC-MS: m/z 481.2 (M + H)+ 600 XII.135 XI.82

LC-MS: m/z 469.05 (M + H)+ 601 XII.136 XI.83

LC-MS: m/z 453.9 (M + H)+ 602 XII.137 VII.114

LC-MS: m/z 433.10 (M + H)+ 603 XII.138 XI.84

LC-MS: m/z 513.2 (M + H)+ 609 XII.139 XI.85

LC-MS: m/z 460.3 (M + H)+ 612 XII.140 XI.86

LC-MS: m/z 431.1 (M + H)+ 613 XII.141 XI.32

LC-MS: m/z 494.2 (M + H)+ 614 XII.142 XI.53

LC-MS: m/z 522.2 (M + H)+ 615 XII.143 XI.87

LC-MS: m/z 511.0 (M + H)+ 616 XII.144 IX.18

LC-MS: m/z 468.1 (M + H)+ 617 XII.145 XI.88

LC-MS: m/z 465.1 (M + H)+ 618 XII.146 XI.89

LC-MS: m/z 449.2 (M + H)+ 619 XII.147 XI.53

LC-MS: m/z 485.2 (M + H)+ 620 XII.148 XI.53

LC-MS: m/z 528.2 (M + H)+ 621 XII.149 XI.53

LC-MS: m/z 528.4 (M + H)+ 622 XII.150 XI.90

LC-MS: m/z 463.0 (M + H)+ 624 XII.151 XI.91

LC-MS: m/z 435.1 (M + H)+ 625 XII.152 XI.53

LC-MS: m/z 447.2 (M + H)+ 626 XII.153 XI.92

LC-MS: m/z 484.2 (M + H)⁺ 627 XII.154 XI.53

LC-MS: m/z 526.3 (M + H)⁺ 628 XII.155 XI.53

¹H NMR (400 MHz, DMSO-d6) δ 8.90- 8.69 (s, 1H), 7.82- 7.79 (m, 1H),7.57- 7.42 (m, 2H), 7.39- 7.35 (m, 2H), 7.14- 7.10 (m, 2H), 6.93 (s,1H), 6.83-6.78 (m, 1H), 6.74 (d, J = 9.2 Hz, 1H), 3.92-3.89 (m, 2H),3.87 (s, 3H), 3.22 (s, 3H), 2.47- 2.30 (m, 1H), 2.13 (s, 3H), 1.80-1.65(m, 6H), 1.48-1.18 (m, 8H), 0.96-0.94 (m, 3H). 630 XII.156 XI.53

1H NMR (400 MHz, DMSO-d6) δ 8.86 (s, 1H), 7.61 (d, J = 2.4 Hz, 1H),7.15-7.07 (m, 4H), 6.95-6.90 (m, 3H), 6.79 (dd, J1 = 2.8 Hz, J2 = 8.8Hz, 1H), 6.64 (d, J = 8.0 Hz, 1H), 3.86 (s, 3H), 3.23 (s, 3H), 2.46-2.42(m, 1H), 2.11 (s, 3H), 1.87- 1.68 (m, 6H), 1.39- 1.30 (m, 5H), 0.87-0.83 (m, 2H), 0.56- 0.52 (m, 2H). 631 XII.157 XI.53

1H NMR (400 MHz, DMSO-d6) δ 8.88 (s, 1H), 7.68 (s, 1H), 7.20-7.12 (m,4H), 6.95-6.92 (m, 3H), 6.80-6.78 (m, 1H), 6.65-6.64 (d, J = 8.4 Hz,1H), 3.84 (s, 3H), 3.22 (s, 3H), 2.24 (s, 1H), 2.20 (s, 3H), 2.10 (s,3H), 1.80- 1.77 (m, 6H), 1.39- 1.33 (m, 4H). 632 XII.158 XI.53

LC-MS: m/z 486.3 (M + H)+ 633 XII.159 XI.53

1H NMR (400 MHz, DMSO-d6) δ 8.70 (s, 1H), 7.36 (d, J = 3.2 Hz, 2H),7.13-7.10 (m, 3H), 6.93-6.91 (m, 3H), 6.75-6.73 (m, 2H), 4.05-4.00 (m,1H), 3.86 (s, 3H), 3.56 (s, 2H), 3.22 (s, 3H), 2.12 (s, 3H), 1.79-1.68(m, 2H), 1.30-1.16 (m, 8H), 0.99 (s, 9H). 634 XII.160 XI.53

1H NMR (400 MHz, DMSO-d6) δ 8.67 (s, 1H), 7.35 (d, J = 2.8 Hz, 1H), 7.10(dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 3H), 7.05 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz,1H), 6.91-6.89 (m, 3H), 6.77 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H), 6.71(d, J = 9.2 Hz, 1H), 4.14- 4.10 (m, 1H), 3.83 (s, 3H), 3.20 (s, 3H),2.45-2.35 (m, 1H), 2.10 (s, 3H), 1.86- 1.67 (m, 7H), 1.50- 1.20 (m,13H). 635 XII.161 XI.53

LC-MS: m/z 444.2 (M − 95)+ COCF3 fragment 636 XII.162 XI.53

LC-MS: m/z 444.20 (M + H)+. 637 XII.163 XI.53

LC-MS: m/z 568.3 (M + H)+ 640 XII.164 XI.53

LC-MS: m/z 456.3 (M − H)+ 641 XII.165 XI.93

LC-MS: m/z 484.1 (M + H)+ 642 XII.166 XI.94

LC-MS: m/z 458.2 (M + H)+ 643 XII.167 XI.81

LC-MS: m/z 431.25 (M + H)+ 646 XII.168 XI.95

LC-MS: m/z 460.2 (M + H)+ 647 XII.169 XI.96

LC-MS: m/z 446.1 (M + H)+ 648 XII.170 XI.32

LC-MS: m/z 416.05 (M + H)+ 649 XII.171 VIII.7

LC-MS: m/z 443.3 (M + H)+ 650 XII.172 VII

LC-MS: m/z 519.2 (M + H)+ 652 XII.173 XI.85

LC-MS: m/z 445.3 (M + H)+ 654 XII.174 XI.80

LC-MS: m/z 447.0 (M + H)+ 655 XII.175 XI.80

LC-MS: m/z 416.2 (M + H)+ 656 XII.176 XI.53

LC-MS: m/z 522.2 (M + H)+ 659 XII.177 XI.97

LC-MS: m/z 465.2 (M + H)+ 660 XII.178 XI.98

LC-MS: m/z 518.1 (M + H)+ 661 XII.179 XI.99

LC-MS: m/z 499.2 (M − H)+ 662 XII.180 XI.99

LC-MS: m/z 469.2 (M + H)+ 663 XII.181 XI.100

LC-MS: m/z 471.2 (M + H)+ 665 XII.182 XI.101

LC-MS: m/z 464.2 (M + H)+ 666 XII.183 XI.101

LC-MS: m/z 463.2 (M + H)+ 669 XII.184 XI.101

LC-MS: m/z 493.2 (M + H)+ 671 XII.185 XI.102

LC-MS: m/z 556.2 (M + H)+ 672 XII.186 XI.101

LC-MS: m/z 519.2 (M + H)+ 673 XII.187 XI.85

LC-MS: m/z 486.25 (M + H)+ 675 XII.188 XI.98

LC-MS: m/z 534.2 (M + H)+ 676 XII.189 XI.98

LC-MS: m/z 503.2 (M + H)+ 677 XII.190 XI.104

LC-MS: m/z 436.1 (M + H)+ 678 XII.191 XI.53

LC-MS: m/z 537.3 (M + H)+ 680 XII.192 XI.103

LC-MS: m/z 464.1 (M + H)+ 681 XII.193 XI.102

LC-MS: m/z 478.2 (M + H)+ 682 XII.194 XI.104

LC-MS: m/z 450.2 (M + H)+

Intermediate-XIII

Step-a: Synthesis of methyl2-((1,4-dioxaspiro[4.5]decan-8-yl)amino)benzoate (XIIIa)

A solution of methyl anthranilate (3 g, 20 mmol, 1 eq.) and1,4-Cyclohexanedione monoethylene acetal (4.6 g, 30 mmol, 1.5 eq.) indichloroethane (50 mL) was added with acetic acid (20 mL) and stirred atRT for 2 h. Reaction mass was cooled to 0° C. and added with sodiumtriacetoxyborohydride (6.3 g, 30 mmol, 1.5 eq.) and allowed to stir atRT for 36 h. Reaction mass was added with saturated bicarbonate solutionand extracted with dichloromethane, purified by combi-flash to affordtitle product (1.01 g, 17%).

¹H NMR (400 MHz, DMSO-d6) δ 7.77 (d, J=7.6 Hz, 1H), 7.71 (d, J=7.6 Hz,1H), 7.39-7.35 (m, 1H), 6.83 (d, J=8.8 Hz, 1H), 6.57-6.53 (m, 1H), 3.87(s, 4H), 3.78 (s, 3H), 3.60-3.58 (m, 1H), 1.95-1.90 (m, 2H), 1.70-1.61(m, 4H), 1.60-1.48 (m, 2H); LC-MS: m/z 292.0 (M+H)⁺

Step-b: Synthesis of methyl 2-((4-oxocyclohexyl)amino)benzoate (XIIIb)

A solution of compound XIIIa (1.01 g, 3.4 mmol, 1 eq.) in acetone (30mL) was added with 2N HCl (10 mL) and allowed to stir at RT overnight.Reaction mass was extracted with ethyl acetate from water andconcentrated in vacuo. The crude was used further without purification.

¹H NMR (400 MHz, DMSO-d6) δ 7.81 (dd, J₁=0.8 Hz, J₂=7.6 Hz, 1H), 7.75(d, J=7.6 Hz, 1H), 6.94 (d, J=8.8 Hz, 1H), 6.59 (t, J=7.6 Hz, 1H),3.97-3.95 (m, 1H), 3.79 (s, 3H), 2.57-2.53 (m, 2H), 2.29-2.19 (m, 4H),1.77-1.72 (m, 2H); LC-MS: m/z 248.2 (M+H)⁺

Step-c: Synthesis of methyl2-((4-((4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl) amino)cyclohexyl)amino) benzoate (Intermediate-XIII)

A solution of compound XIIIb (0.5 g, 2.02 mmol, 1 eq.) andIntermediate-I (0.53 g, 2.02 mmol, 1 eq.) in acetic acid (10 mL) wasadded with sodium triacetoxyborohydride (1.28 g, 6.06 mmol, 3 eq.) andheated at 8° C. for 16 h. Reaction mass was extracted with ethyl acetatefrom sat. bicarbonate and brine and concentrated in vacuo. Crude waspurified by combi-flash to afford title compound as pale pink liquid(0.67 g, 67%). LC-MS: m/z 493.3 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-XIII using appropriate reactants and reagents and inpresence of suitable solvents and appropriate reaction conditions.

Interme- diate Re- CP No. actant Structure Analytical data 102, 103XIII.1 Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 7.27 (s, 1H), 7.02 (dd, J₁ = 2.4 Hz, J₂ =8.8 Hz, 1H), 6.98 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 1H), 6.61(d, J = 8.8 Hz, 2H), 5.74 (s, 1H), 4.15-4.03 (m, 2H), 3.52 (m, 1H), 3.39(s, 1H), 2.31-2.18 (m, 3H), 2.07 (s, 3H), 1.98-1.92 (m, 1H), 1.84 (s,6H), 1.81-1.61 (m, 9H), 1.18 (t, J = 7.2 Hz, 3H), 1.12-1.05 (m, 1H).LC-MS: m/z 507.2 (M + H)⁺ 128, 129 XIII.2 XI.1

LC-MS: m/z 561.2 (M + H)⁺ 130 XIII.3 Int-I.1

LC-MS: m/z 368.2 (M + H)⁺ 131 XIII.4 Int-I.1

¹H NMR (400 MHz, DMSO-d6) δ 7.02 (d, J = 8.4 Hz, 2H), 6.59 (d, J = 8.8Hz, 2H), 5.01 (d, J = 9.6 Hz, 1H), 3.98-3.88 (m, 3H), 2.75-2.68 (m, 1H),2.08 (s, 3H), 2.00- 1.82 (m, 1H), 1.77 (m, 8H), 1.73-1.46 (m, 4H),1.36-1.23 (m, 2H), 1.07 (t, J = 7.6 Hz, 3H). LC- MS: m/z 382.2 (M + H)⁺136 XIII.5 Int-XI

LC-MS: m/z 507.3 (M + H)⁺ 162 XIII.6 Int-XI

LC-MS: m/z 608.2 (M + H)⁺ 172 XIII.7 Int-XI

LC-MS: m/z 594.2 (M + H)⁺ 244 XIII.8 Int-I

LC-MS: m/z 375.1 (M − 55)⁺ Boc fragment 248 XIII.9 Int-I

¹H NMR (400 MHz, DMSO- d6) δ 7.19 (d, J = 1.9 Hz, 1H), 7.13 (d, J = 8.8Hz, 1H), 6.76 (d, J = 8.8 Hz, 1H), 4.65-4.63 (m, 1H), 3.61-3.60 (m, 2H),3.37- 3.36 (m, 1H), 3.15-3.08 (m, 2H), 2.02 (bs, 3H), 1.89-1.88 (m, 1H),1.73 (s, 6H), 1.70 (s, 6H), 1.63- 1.62 (m, 2H), 1.26 (s, 9H). 244XIII.10 XIII.8

¹H NMR (400 MHz, DMSO- d6) δ 8.60 (s, 1H), 8.00 (s, 1H), 7.40 (s, 1H),7.18 (d, J = 2.0 Hz, 1H), 7.11 (dd, J₁ = 2.0 Hz, J₂ = 8.8 Hz, 1H), 6.63(d, J = 8.8 Hz, 1H), 4.60 (s, 1H), 3.97-3.89 (bs, 1H), 3.84 (s, 3H),2.02 (s, 3H), 1.77 (s, 6H), 1.67 (s, 6H). LC-MS: m/z 480.1 (M + H)⁺ 248XIII.11 XIII.9

LC-MS: m/z 494.1 (M + H)⁺ 567 XIII.12 XII.105

LC-MS: m/z 460.3 (M + H)+.

Intermediate-XIV

Step-a: Synthesis of 4-((2-(methoxycarbonyl)phenyl)amino)benzoic acid(Intermediate-XIV)

A solution of Intermediate-II.20 (3 g, 9.1 mmol, 1 eq.) in DCM (30 mL)was cooled in ice for 10 minutes. TFA (3 mL) was added drop wise andallowed to stir at RT for 16 h. Reaction mass was concentrated in vacuo.The crude was triturated with n-pentane and dried in vacuo to affordtitle product as pale green solid (2.0 g, 800).

¹H NMR (400 MHz, DMSO-d6) δ 12.58 (s, 1H), 9.40 (s, 1H), 7.93 (dd,J₁=0.6 Hz, J₂=8.0 Hz, 1H), 7.87 (dd, J₁=2.0 Hz, J₂=6.8 Hz, 2H),7.52-7.46 (m, 2H), 7.26 (d, J=8.8 Hz, 2H), 7.01-6.97 (m, 1H), 3.84 (s,3H); LC-MS: m/z 272.1 (M+H)⁺

Alternate or General Procedure for Synthesizing the CorrespondingCarboxylic Acid Compounds which are Having Methyl & Ethyl Esters

To a solution of ester (1 mmol) in THF:MeH:H₂O (4+4+2 mL), LiOH.H₂O (5mmol) was added and stirred at RT for 16 h. Reaction mass wasconcentrated in vacuo, diluted with water and acidified with 2 N HCl topH 5. The precipitate obtained was filtered and dried under vacuum. Thissolid was washed with 10% ether in hexane mixture and dried to afforddesired acid.

The below intermediates were prepared by a procedure similar toIntermediate-XIV using appropriate reactants and reagents and inpresence of suitable solvents and appropriate reaction conditions.

Interme- diate CP No. Reactant Structure Analytical data 106, 107, 145,215 XIV.1 VII.6

¹H NMR (400 MHz, DMSO-d6) δ 12.26 (s, 1H), 8.27 (s, 1H), 7.75 (d, J =8.8 Hz, 1H), 7.43 (s, 1H), 7.35-7.3 (m, 2H), 6.86 (d, J = 8.9 Hz, 2H),2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 382.1 (M + H)⁺254, 301 XIV.2 II.15

¹H NMR (400 MHz, DMSO-d6) δ 12.59 (s, 1H), 10.38 (s, 1H), 8.49 (dd, J₁ =1.9 Hz, J₂ = 4.4 Hz, 1H), 8.31 (dd, J₁ = 2.0 Hz, J₂ = 5.8 Hz, 1H), 7.89(m, 4H), 7.0 (m, 1H), 3.92 (s, 3H). 255 XIV.3 V.4

¹H NMR (400 MHz, DMSO-d6) δ 7.9-7.8 (m, 1H), 7.80-7.70 (m, 1H), 7.64 (d,J = 9.6 Hz, 2H), 7.52-7.40 (m, 2H), 6.47 (d, J = 9.2 Hz, 2H), 3.55 (s,3H), 3.24 (s, 3H), 1.49 (s, 9H). LC-MS: m/z 286.1 (M + H)⁺ 258 XIV.4 V.5

¹H NMR (400 MHz, DMSO-d6) δ 8.57 (dd, J₁ = 2.0 Hz, J₂ = 4.9 Hz, 1H),8.01 (dd, J₁ = 1.4 Hz, J₂ = 7.3 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H),7.23-7.20 (m, 3H). 259, 346 XIV.5 II.16

¹H NMR (400 MHz, DMSO-d6) δ 12.5 (s, 1H), 9.75 (s, 1H), 7.97 (d, J = 8.8Hz, 2H), 7.85 (d, J = 8.8 Hz, 2H), 7.79 (m, 1H), 7.53 (d, J = 6.8 Hz,1H), 7.14 (d, J = 8.3 Hz, 1H), 4.35 (m, 2H), 1.38 (t, J = 2.0 Hz, 3H).265 XIV.6 II.18

¹H NMR (400 MHz, DMSO-d6) δ 12.64 (s, 1H), 9.29 (s, 1H), 8.11 (dd, J₁ =1.6 Hz, J₂ = 8.4 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.63-7.58 (m, 1H),7.50- 7.46 (m, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.12-7.06 (m, 1H). LC-MS:m/z 257.1 (M − H)⁻. 293, 294, 276 XIV.7 VI.44

¹H NMR (400 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.68 (s, 1H), 7.89 (d, J = 6.9Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.41-7.40 (m, 1H), 7.23-7.20 (m, 4H),7.11 (d, J = 8.3 Hz, 1H), 7.03 (d, J = 8.8 Hz, 2H), 6.76 (t, J = 7.6 Hz,1H), 3.86 (s, 3H). 302 XIV.8 II.21

¹H NMR (400 MHz, DMSO-d6) δ 12.2 (s, 1H), 10.05 (s, 1H), 8.41-8.40 (m,1H), 8.26 (d, J = 7.8 Hz, 2H), 7.64 (d, J = 8.3 Hz, 2H), 7.22 (d, J =1.9 Hz, 2H), 6.92-6.89 (m, 1H), 3.90 (s, 3H), 3.52 (s, 3H). 303 XIV.9II.22

¹H NMR (400 MHz, DMSO-d6) δ 12.4 (s, 1H), 8.92 (s, 1H), 7.82 (d, J = 8.8Hz, 2H), 7.74 (s, 1H), 7.54-7.52 (m, 2H), 7.45-7.44 (m, 2H), 7.09 (d, J= 8.8 Hz, 2H), 3.84 (s, 3H). LC-MS: m/z 272.0 (M + H)⁺ 315, 316 XIV.10II.35

LC-MS: m/z 348.1 (M + H)⁺ 330 XIV.11 II.24

¹H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 8.10 (t, J = 7.8 Hz, 1H),7.99 (d, J = 8.3 Hz, 2H), 7.88 (d, J = 7.4 Hz, 1H), 7.38 (d, J = 8.3 Hz,1H), 7.26 (d, J = 8.3 Hz, 2H), 3.82 (s, 3H). LC-MS: m/z 274.0 (M + H)⁺333, 341, 395, 408 XIV.12 II.25

¹H NMR (400 MHz, DMSO-d6) δ 13.01 (s, 1H), 9.32 (s, 1H), 7.92-7.90 (m,1H), 7.77-7.76 (m, 1H), 7.62-7.60 (m, 1H), 7.48- 7.44 (m, 3H), 7.28-7.24(m, 1H), 6.90-6.86 (m, 1H), 3.89 (s, 3H). LC-MS: m/z 272.1 (M + H)⁺ 334XIV.13 II.26

¹H NMR (400 MHz, DMSO-d6) δ 12.79 (s, 1H), 7.93-7.90 (m, 3H), 7.71-7.67(m, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 6.93 (d, J= 8.8 Hz, 2H), 3.67 (s, 3H). LC-MS: m/z 273.1 (M + H)⁺ 353 XIV.14 V.7

¹H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 7.78 (d, J = 7.2 Hz, 1H),7.67 (t, J = 7.6 Hz, 1H), 7.42-7.37 (m, 2H), 7.27-7.21 (m, 2H), 7.07 (s,1H), 6.77 (d, J = 7.2 Hz, 1H), 3.50 (s, 3H), 3.22 (s, 3H). LC-MS: m/z284.1 (M + H)⁺ 357 XIV.15 V.9

LC-MS: m/z 391.2 (M + H)⁺ 394 XIV.16 II.34

¹H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 8.45 (dd, J₁ = 2.0 Hz, J₂ =4.8 Hz, 1H), 8.34 (t, J = 2.0 Hz, 1H), 8.28 (dd, J₁ = 2.0 Hz, J₂ = 8.0Hz, 1H), 7.92-7.90 (m, 1H), 7.62-7.59 (m, 1H), 7.45 (t, J = 8.0 Hz, 1H),6.94 (dd, J₁ = 4.8 Hz, J₂ = 7.6 Hz, 1H), 3.91 (s, 3H). LC-MS: m/z 273.1(M + H)⁺ 363 XIV.17 II.33

¹H NMR (400 MHz, DMSO-d6) δ 12.81 (s, 1H), 8.25 (s, 1H), 7.60 (s, 1H),7.33-7.21 (m, 5H), 7.04 (d, J = 8.4 Hz, 2H), 2.04 (s, 3H), 1.84 (s, 6H),1.72 (s, 6H). LC-MS: m/z 348.1 (M + H)⁺ 386, 387 XIV.18 VI.62

¹H NMR (400 MHz, DMSO-d6) δ 10.02 (s, 1H), 8.64 (s, 1H), 8.39-8.38 (m,1H), 8.26-8.24 (m, 1H), 7.76 (d, J = 6.8 Hz, 2H), 7.66-7.63 (m, 2H),7.18-7.15 (m, 2H), 6.99-6.97 (m, 2H), 6.86 (dd, J₁ = 4.8 Hz, J₂ = 8.0Hz, 1H), 3.90 (s, 3H). LC-MS: m/z 364.2 (M + H)⁺ 638 XIV.19 II.29

LC-MS: m/z 296.2 (M + H)+ 651 XIV.20 II.28

LC-MS: m/z 310.05 (M + H)+

Intermediate-XV

Step-a: Synthesis of methyl2-(4-(4-((3R,5S)-adamantan-1-yl)phenyl)carbamoyl) phenyl) amino)benzoate(Intermediate-XV)

A solution of compound-XIV (0.2 g, 0.74 mmol, 1 eq.) andIntermediate-I.1 (0.185 g, 0.81 mmol, 1.1 eq.) was cooled in ice. HATU(0.34 g, 0.89 mmol, 1.2 eq.) followed by DIPEA (0.39 mL, 2.22 mmol, 3eq.) were added and allowed to stir at RT for 16 h. Reaction mass wasadded to ice water slowly under stirring. The obtained precipitate wasfiltered, washed with cold water twice followed by n-pentane twice anddried in vacuo to afford title compound as cream coloured solid (0.35 g,98%).

¹H NM/R (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 9.43 (s, 1H), 7.96-7.91 (m,3H), 7.69 (d, J=8.4 Hz, 2H), 7.54-7.49 (m, 1H), 7.45 (d, J=8.0 Hz, 1H),7.34-7.31 (m, 4H), 6.95 (t, J=6.8 Hz, 1H), 3.86 (s, 3H), 2.06 (s, 3H),1.87 (s, 6H), 1.74 (s, 6H); LC-MS: m/z 481.1 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-XV using appropriate reactants and reagents and in presenceof suitable solvents and appropriate reaction conditions.

Interme- diate CP No. Reactant Structure Analytical data 71 XV.1 Int-XIV& I.4

LC-MS: m/z 560.1 (M + H)⁺ 106 XV.2 XIV.1

¹H NMR (400 MHz, DMSO- d6) δ 8.03 (s, 1H), 7.47-7.4 (m, 3H), 7.33-7.27(m, 2H), 6.9 (d, J = 8.3 Hz, 2H), 4.46- 4.44 (m, 1H), 3.64-3.61 (m, 5H),2.32 (m, 1H), 2.05 (s, 3H), 1.85 (s, 9H), 1.73 (s, 6H). LC-MS: m/z 493.2(M + H)⁺ 107 XV.3 XIV.1

¹H NMR (400 MHz, DMSO- d6) δ 8.03 (s, 1H), 7.47-7.4 (m, 3H), 7.33-7.27(m, 2H), 6.9 (d, J = 8.3 Hz, 2H), 4.46- 4.44 (m, 1H), 3.64-3.61 (m, 5H),2.32 (m, 1H), 2.05 (s, 3H), 1.85 (s, 9H), 1.73 (s, 6H). LC-MS: m/z 493.2(M + H)⁺ 109 XV.4 Int-XI

LC-MS: m/z 584.2 (M + H)⁺ 145 XV.5 XIV.1

¹H NMR (400 MHz, DMSO- d6) δ 7.99 (s, 1H), 7.85 (d, J = 7.8 Hz, 1H),7.65 (d, J = 8.8 Hz, 2H), 7.39 (s, 1H), 7.29-7.28 (m, 2H), 6.90 (d, J =8.8 Hz, 2H), 4.60-4.58 (m, 1H), 3.91-3.87 (m, 2H), 3.02-2.98 (m, 1H),2.05 (s, 3H), 1.97-1.76 (m, 10H), 1.72 (s, 6H), 1.40-1.30 (m, 2H), 0.88(t, J = 7.2 Hz, 3H). LC-MS: m/z 521.1 (M + H)⁺ 161 XV.6 I.16

LC-MS: m/z 381 (M + H)⁺ 186 XV.7 Int-XI

LC-MS: m/z 539.1 (M + H)⁺ 212 XV.8 XI.1

¹H NMR (400 MHz, DMSO- d6) δ 10.36 (s, 1H), 8.15 (s, 1H), 7.55 (s, 1H),7.43 (d, J = 1.2 Hz, 2H), 7.31 (d, J = 0.8 Hz, 2H), 6.94 (s, 1H), 4.88(d, J = 5.2 Hz, 1H), 4.76 (d, J = 5.2 Hz, 1H), 3.71 (s, 3H), 2.06 (s,3H), 1.86 (s, 6H), 1.73 (s, 6H), 1.42 (d, J = 3.2 Hz, 6H), LC-MS: m/z607.2 (M + H)⁺ 215 XV.9 XIV.1

LC-MS: m/z 507.3 (M + H)⁺ 230 XV.10 Int-XI

LC-MS: m/z 536.3 (M + H)⁺ 254 XV.11 XIV.2

¹H NMR (400 MHz, DMSO- d6) δ δ 10.35 (s, 1H), 10.02 (s, 1H), 8.51 (dd,J₁ = 2.0 Hz, J2 = 4.5 Hz, 1H), 8.31 (dd, J1 = 2.0 Hz, J₂ = 7.8 Hz, 1H),7.96 (d, J = 8.8 Hz, 2H), 7.89 (d, J = 8.8 Hz, 2H), 7.69 (d, J = 8.3 Hz,2H), 7.32 (d, J = 8.8 Hz, 2H), 6.99 (m, 1H), 3.92 (s, 3H), 2.06 (s, 3H),1.82 (s, 6H), 1.74 (s, 6H). 255 XV.12 XIV.3

¹H NMR (400 MHz, DMSO- d6) δ 9.79 (s, 1H), 7.84 (dd, J1 = 1.2 Hz, J2 =7.6 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.73-7.69 (m, 1H), 7.65 (d, J =8.8 Hz, 2H), 7.48-7.40 (m, 2H), 7.28 (d, J = 8.8 Hz, 2H), 6.53 (d, J =8.8 Hz, 2H), 3.57 (s, 3H), 3.27 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H),1.73 (s, 6H), LC-MS: m/z 495.1 (M + H)⁺ 258 XV.13 XIV.4

¹H NMR (400 MHz, DMSO- d6) δ δ 9.98 (s, 1H), 8.5 (m, 1H), 7.97 (d, J =7.3 Hz, 1H), 7.87 (d, J = 8.3 Hz, 2H), 7.68 (d, J = 8.3 Hz, 2H), 7.3 (d,J = 8.8 Hz, 2H), 7.18-7 (m, 1H), 6.98 (d, J = 8.8 Hz, 2H), 3.48 (s, 3H),3.32 (s, 3H), 2.05 (s, 3H), 1.83 (s, 6H), 1.73 (s, 6H). 259 XV.14 XIV.5

¹H NMR (400 MHz, DMSO- d6) δ δ 9.99 (s, 1H), 9.7 (s, 1H), 8.01 (d, J =9.3 Hz, 2H), 7.93 (d, J = 8.8 Hz, 2H), 7.81 (m, 1H), 7.69 (d, J = 8.8Hz, 2H), 7.52 (d, J = 6.8 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H), 7.13 (d, J= 8.3 Hz, 1H), 4.35 (m, 2H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H),1.38 (t, J = 7.4 Hz, 3H). 272 XV.15 XI.13

¹H NMR (400 MHz, DMSO- d6) δ δ 10.17 (s, 1H), 9.28 (s, 1H), 7.91-7.88(m, 3H), 7.78 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.42- 7.38(m, 1H), 7.24 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.0 Hz, 1H), 6.66-6.65(m, 1H), 3.86 (s, 3H), 2.08 (s, 3H), 1.90 (s, 6H), 1.76 (s, 6H). LC-MS:m/z 479.0 (M − H)⁻. 274 XV.16 Int-XIV

¹H NMR (400 MHz, DMSO- d6) δ 9.34 (s, 1H), 7.92 (dd, J₁ = 1.5 Hz, J₂ =7.8 Hz, 1H), 7.46 (t, J = 1.5 Hz, 1H), 7.30-7.20 (m, 5H), 6.90-6.86 (m,1H), 3.89 (s, 3H), 3.40- 3.30 (m, 4H), 1.52-1.49 (m, 4H), 1.12-1.08 (m,4H), 0.84-0.78 (m, 6H). 285 XV.17 Int-XIV

¹H NMR (400 MHz, DMSO- d6) δ δ 9.38 (s, 1H), 7.92 (d, J = 6.8 Hz, 1H),7.78 (d, J = 8.0 Hz, 2H), 7.50-7.43 (m, 2H), 7.37 (d, J = 8.0 Hz, 1H),7.27-7.23 (m, 2H), 6.91 (t, J = 7.6 Hz, 1H), 3.85 (s, 3H), 2.07 (s, 9H),1.66 (s, 6H), 1.66 (s, 6H). LC-MS: m/z 405.1 (M + H)⁺ 288 XV.18 Int-XIV

¹H NMR (400 MHz, DMSO- d6) δ 9.78 (s, 1H), 9.42 (s, 1H), 7.92 (d, J =6.8 Hz, 3H), 7.52-7.50 (m, 3H), 7.44 (d, J = 7.3 Hz, 1H), 7.31 (d, J =8.8 Hz, 2H), 6.94 (t, J = 6.8 Hz, 1H), 6.63 (d, J = 9.3 Hz, 2H), 3.86(s, 3H), 3.23 (t, J = 7.2 Hz, 4H), 1.50-1.45 (m, 4H), 1.34-1.30 (m, 4H),0.89 (t, J = 7.2 Hz, 6H). 293, 276 XV.19 XIV.7

¹H NMR (400 MHz, DMSO- d6) δ 9.20 (s, 1H), 8.38 (s, 1H), 7.88 (dd, J₁ =1.4 Hz, J₂ = 7.8 Hz, 1H), 7.37-7.36 (m, 1H), 7.19-7.16 (m, 6H),7.05-7.04 (m, 3H), 6.75- 6.71 (m, 1H), 3.85 (s, 3H), 3.32-3.30 (m, 4H),1.52-1.49 (m, 4H), 1.23-1.22 (m, 4H), 0.85-0.84 (m, 6H). 294 XV.20 XIV.7

¹H NMR (400 MHz, DMSO- d6) δ 9.21 (s, 1H), 8.47 (s, 1H), 7.89-7.87 (dd,J1 = 1.6 Hz, J2 = 7.6 Hz, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.36 (t, J =8.4 Hz, 1H), 7.24 (s, 1H), 7.21-7.14 (m, 4H), 7.06 (d, J = 8.0 Hz, 1H),7.0 (d, J = 8.8 Hz, 2H), 6.74 (t, J = 7.6 Hz, 1H), 3.86 (s, 3H), 2.06(s, 9H), 1.65 (s, 6H). LC- MS: m/z 496.0 (M + H)⁺ 297 XV.21 VII.14

¹H NMR (400 MHz, DMSO- d6) δ 10.09 (s, 1H), 9.29 (s, 1H), 7.90 (d, J =8.3 Hz, 2H), 7.83 (d, J = 6.3 Hz, 2H), 7.72-7.7 (m, 3H), 7.51 (d, J =8.3 Hz, 2H), 7.40 (d, J = 7.3 Hz, 1H), 7.03 (d, J = 8.3 Hz, 1H),4.35-4.34 (m, 2H), 2.08 (s, 3H), 1.93 (s, 6H), 1.76 (s, 6H), 1.37 (t, J= 7.4 Hz, 3H). 301 XV.22 XIV.2

LC-MS: m/z 516.0 (M + H)⁺ 302 XV.23 XIV.8

¹H NMR (400 MHz, DMSO- d6) δ 10.05 (s, 1H), 10.03 (s, 1H), 8.41-8.40 (m,1H), 8.26-8.25 (m, 1H), 7.65 (d, J = 8.3 Hz, 2H), 7.52 (d, J = 8.8 Hz,2H), 7.27-7.26 (m, 4H), 6.88-6.87 (m, 1H), 3.89 (s, 3H), 3.57 (s, 2H),2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). 303 XV.24 XIV.9

¹H NMR (400 MHz, DMSO- d6) δ 9.92 (s, 1H), 8.85 (s, 1H), 7.89 (d, J =8.0 Hz, 2H), 7.75 (s, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.51-7.43 (m, 3H),7.30 (d, J = 8.8 Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H), 2.06(s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 481.3 (M + H)⁺ 313 XV.25Int-XIV

¹H NMR (400 MHz, DMSO- d6) δ 10.04 (s, 1H), 9.43 (s, 1H), 7.96-7.94 (m,3H), 7.72 (d, J = 8.8 Hz, 2H), 7.51 (m, 1H), 7.46 (d, J = 7.3 Hz, 1H),7.34 (d, J = 8.3 Hz, 2H), 7.20 (t, J = 7.4 Hz, 2H), 7.05 (d, J = 8.8 Hz,2H), 7.93 (t, J = 6.9 Hz, 1H), 6.82 (m, 3H), 3.86 (s, 3H), 3.65 (t, J =7.3 Hz, 2H), 1.56-1.55 (m, 2H), 1.37-1.36 (m, 2H), 0.88 (t, J = 3.9 Hz,3H). 315 XV.26 XIV.10

¹H NMR (400 MHz, DMSO- d6) δ 11.53 (s, 1H), 8.66 (d, J = 7.4 Hz, 2H),8.03 (d, J = 6.8 Hz, 1H), 7.82 (d, J = 8.8 Hz, 2H), 7.66-7.65 (m, 1H),7.32 (d, J = 8.8 Hz, 2H), 7.21-7.10 (m, 5H), 3.91 (s, 3H), 2.06 (s, 3H),1.89 (s, 6H), 1.71 (s, 6H). 316 XV.27 XIV.10

¹H NMR (400 MHz, DMSO- d6) δ 10.13 (s, 1H), 8.56 (s, 1H), 8.45 (s, 1H),8.07 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 8.3 Hz, 2H), 7.66 (d, J = 13 Hz,1H), 7.47 (t, J = 7.9 Hz, 1H), 7.31 (d, J = 8.3 Hz, 2H), 7.14 (d, J =8.8 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 3.87 (s, 3H), 2.06 (s, 3H), 1.82(s, 6H), 1.74 (s, 6H). 324 XV.28 XIV.5

¹H NMR (400 MHz, DMSO- d6) δ 9.47 (s, 1H), 7.75-7.67 (m, 2H), 7.45 (d, J= 7.6 Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H),7.09-7.02 (m, 3H), 6.47 (d, J = 8.8 Hz, 1H), 4.30 (q, J = 6.8 Hz, 2H),3.33 (s, 3H), 2.01 (s, 3H), 1.8-0 (s, 6H), 1.70 (s, 6H), 1.32 (t, J =6.8 Hz, 3H). LC-MS: m/z 510.3 (M + H)⁺ 329 XV.29 Int-XIV

¹H NMR (400 MHz, DMSO- d6) δ 10.17 (s, 1H), 9.45 (s, 1H), 7.99-7.93 (m,3H), 7.83 (d, J = 8.4 Hz, 2H), 7.52- 7.40 (m, 3H), 7.36-7.34 (m, 3H),7.26-7.21 (m, 3H), 7.13 (d, J = 6.8 Hz, 1H), 7.00- 6.90 (m, 1H), 3.87(s, 3H), 3.10-3.00 (m, 1H), 1.13 (d, J = 6.8 Hz, 6H). LC-MS: m/z 465.1(M + H)⁺ 330 XV.30 XIV.11

¹H NMR (400 MHz, DMSO- d6) δ 10.20 (s, 1H), 8.12- 8.08 (m, 1H), 8.02(dd, J₁ = 2.0 Hz, J₂ = 6.8 Hz, 2H), 7.88 (dd, J₁ = 4.0 Hz, J₂ = 8.0 Hz,1H), 7.70 (d, J = 8.0 Hz, 2H), 7.40-7.37 (m, 1H), 7.33 (dd, J₁ = 0.8 Hz,J₂ = 2.0 Hz, 4H), 3.82 (s, 3H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s,6H). LC-MS: m/z 483.1 (M + H)⁺ 333 XV.31 XIV.13

¹H NMR (400 MHz, DMSO- d6) δ 10.15 (s, 1H), 9.40 (s, 1H), 7.92 (d, J =8.0 Hz, 1H), 7.79 (s, 1H), 7.69-7.62 (m, 3H), 7.50-7.46 (m, 3H),7.33-7.29 (m, 3H), 6.90-6.80 (m, 1H), 3.87 (s, 3H), 2.06 (s, 3H), 1.86(s, 6H), 1.74 (s, 6H). LC-MS: m/z 481.2 (M + H)⁺ 334 XV.32 XIV.14

¹H NMR (400 MHz, DMSO- d6) δ 10.08 (s, 1H), 7.96 (d, J = 8.3 Hz, 2H),7.91 (d, J = 6.8 Hz, 1H), 7.68-7.66 (m, 3H), 7.40-7.37 (m, 1H), 7.32 (d,J = 8.8 Hz, 2H), 7.20 (d, J = 7.8 Hz, 1H), 6.98 (d, J = 8.3 Hz, 2H),3.70 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 482.3(M + H)⁺ 335 XV.33 Int-XIV

¹H NMR (400 MHz, DMSO- d6) δ 10.0 (s, 1H), 9.43 (s, 1H), 7.96-7.92 (m,3H), 7.68 (d, J = 8.8 Hz, 2H), 7.51- 7.49 (m, 1H), 7.44 (d, J = 8.4 Hz,1H), 7.33-7.29 (m, 4H), 6.95 (t, J = 7.6 Hz, 1H), 3.86 (s, 3H), 2.14 (m,1H), 1.69 (s, 2H), 1.53-1.33 (m, 8H), 1.19 (s, 2H), 0.86 (s, 6H). LC-MS:m/z 509.3 (M + H)⁺ 336 XV.34 XIV.10

LC-MS: m/z 482.2 (M + H)⁺ 341 XV.35 XIV.13

¹H NMR (400 MHz, DMSO- d6) δ 10.14 (s, 1H), 9.40 (s, 1H), 7.92 (d, J =8.0 Hz, 1H), 7.80 (s, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.64 (d, J = 7.2Hz, 1H), 7.51-7.44 (m, 3H), 7.32-7.30 (m, 3H), 6.87 (t, J = 8.0 Hz, 1H),3.87 (s, 3H), 2.14 (s, 1H), 1.68 (s, 2H), 1.53-1.33 (m, 8H), 1.19 (s,2H), 0.86 (s, 6H). LC-MS: m/z 509.3 (M + H)⁺ 343 XV.36 XIV.13

¹H NMR (400 MHz, DMSO- d6) δ 10.32 (s, 1H), 9.42 (s, 1H), 7.93 (d, J =8.0 Hz, 1H), 7.84-7.82 (m, 3H), 7.66 (d, J = 6.8 Hz, 1H), 7.54- 7.12 (m,10H), 6.88 (t, J = 7.20 Hz, 1H), 3.87 (s, 3H), 2.04-2.01 (m, 1H), 1.12(d, J = 6.8 Hz, 6H). LC-MS: m/z 465.1 (M + H)⁺ 344 XV.37 Int-I.1

¹H NMR (400 MHz, DMSO- d6) δ 11.64 (s, 1H), 10.36 (s, 1H), 8.53 (dd, J₁= 0.8 Hz, J₂ = 8.4 Hz, 1H), 8.14-8.08 (m, 4H), 8.03 (dd, J₁ = 1.6 Hz, J₂= 8.0 Hz, 1H), 7.73- 7.71 (m, 3H), 7.36-7.34 (m, 2H), 7.30-7.25 (m, 1H),3.90 (s, 3H), 2.07 (s, 3H), 1.87 (d, J = 2.4 Hz, 6H), 1.74 (s, 6H).LC-MS: m/z 509.3 (M + H)⁺ 346 XV.38 XIV.5

¹H NMR (400 MHz, DMSO- d6) δ 9.94 (s, 1H), 9.70 (s, 1H), 8.00 (d, J =8.8 Hz, 2H), 7.93 (d, J = 8.8 Hz, 2H), 7.79 (t, J = 7.6 Hz, 1H), 7.69(d, J = 8.8 Hz, 2H), 7.51 (d, J = 7.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H),7.13 (d, J = 8.0 Hz, 1H), 4.38-4.33 (m, 2H), 2.14 (m, 1H), 1.69 (s, 2H),1.53-1.33 (m, 11H), 1.19 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 524.3 (M +H)⁺ 353 XV.39 XIV.15

LC-MS: m/z 495.1 (M + H)⁺ 363 XV.40 XIV.18

¹H NMR (400 MHz, DMSO- d6) δ 11.61 (s, 1H), 8.61 (d, J = 8.4 Hz, 1H),8.38 (s, 1H), 8.02 (d, J = 7.2 Hz, 1H), 7.70-7.63 (m, 2H), 7.42-7.22 (m,6H), 7.11 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H),1.73 (s, 6H). LC-MS: m/z 481.2 (M + H)⁺ 364 XV.41 XIV.18

¹H NMR (400 MHz, DMSO- 10.39 (s, 1H), 8.46 (t, J = 2.0 Hz, 1H), 8.29 (s,1H), 8.04 (dd, J₁ = 0.8 Hz, J₂ = 8.0 Hz, 1H), 7.69-7.67 (m, 1H), 7.59(s, 1H), 7.49 (t, J = 8.0 Hz, 1H), 7.36-7.20 (m, 5H), 7.08 (d, J = 8.8Hz, 2H), 3.87 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS:m/z 481.2 (M + H)⁺ 368 XV.42

LC-MS: m/z 523.3 (M + H)⁺ 369 XV.43

LC-MS: m/z 509.2 (M + H)⁺ 386 XV.44 XIV.19

¹H NMR (400 MHz, DMSO- d6) δ 9.97 (s, 1H), 8.38 (dd, J₁ = 2.0 Hz, J₂ =4.8 Hz, 1H), 8.33 (s, 1H), 8.24 (dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H), 7.60(d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 3.2 Hz, 2H),6.99 (d, J = 8.8 Hz, 2H), 6.84 (dd, J₁ = 2.8 Hz, J₂ = 8.0 Hz, 1H), 3.90(s, 3H), 3.29 (s, 6H), 1.54-1.47 (m, 4H), 1.23-1.20 (m, 4H), 0.85 (s,6H). LC-MS: m/z 475.3 (M + H)⁺ 387 XV.45 XIV.19

¹H NMR (400 MHz, DMSO- d6) δ 9.97 (s, 1H), 8.39-8.38 (m, 2H), 8.24 (dd,J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H), 7.64 (dd, J₁ = 8.4 Hz, J₂ = 19.2 Hz, 4H),7.21 (s, 1H), 7.12 (d, J = 8.8 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 6.84(dd, J₁ = 4.8 Hz, J₂ = 8.0 Hz, 1H), 3.90 (s, 3H), 1.99 (s, 10H), 1.65(s, 6H). LC-MS: m/z 497.3 (M + H)⁺ 394 XV.46 XIV.17 & I.3

LC-MS: m/z 544.3 (M + H)⁺ 407 XV.47 Int-XIV & I.29

¹H NMR (400 MHz, DMSO- d6) δ 9.41 (s, 1H), 8.89 (t, J = 6.0 Hz, 1H),7.93-7.91 (m, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.51-7.48 (m, 1H),7.43-7.40 (m, 1H), 7.33-7.22 (m, 6H), 6.95-6.91 (m, 1H), 4.43 (d, J =6.0 Hz, 2H), 3.84 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H),LC-MS: m/z 495.3 (M + H)⁺ 408 XV.48 XIV.13 & I.29

¹H NMR (400 MHz, DMSO- d6) δ 9.39 (s, 1H), 9.02 (t, J = 6.0 Hz, 1H),7.95-7.90 (m, 1H), 7.76 (s, 1H), 7.60- 7.55 (m, 1H), 7.45-7.42 (m, 3H),7.32-7.23 (m, 5H), 6.87-6.83 (m, 1H), 4.42 (d, J = 6.0 Hz, 2H), 3.86 (s,3H), 2.04 (s, 3H), 1.84 (s, 6H), 1.76 (s, 6H), LC-MS: m/z 495.3 (M + H)⁺638 XV.49 XIV.20

LC-MS: m/z 429.2 (M + H)+ 651 XV.50 XIV.21

LC-MS: m/z 443.2 (M + H)+ 664 XV.51 XIV.13

LC-MS: m/z 429.1 (M + H)+

Intermediate-XVI

Step-a: Synthesis of N-(4-(N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl)sulfamoyl)phenyl) acetamide (Intermediate-XVI)

A solution of Intermediate-I.1 (0.5 g, 2.2 mmol) in dichloromethane (10mL) was cooled to ° C. and added with triethylamine (0.66 g, 6.6 mmol, 3eq.) followed by 4-acetamidobenzenesulfonyl chloride (0.51 g, 2.2 mmol)and stirred at RT for 3 h. Reaction mass was concentrated in vacuo andadded with cold water. The obtained solid was filtered and dried undervacuum to afford title product (0.88 g, 94%). LC-MS: m/z 425.1 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-XVI using appropriate reactants and reagents and inpresence of suitable solvents and appropriate reaction conditions.

Inter- mediate CP No. Reactant Structure Analytical data 372 XVI.1Int-I.1

LC-MS: m/z 411.1 (M − H)⁻ 393, 392 XVI.2 Int-I

¹H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H), 8.80 (dd, J = 1.6 Hz, J₂ = 6.4Hz, 1H), 8.31- 8.30 (m, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.63 (d, J = 9.2Hz, 2H), 7.29 (d, J = 2.8 Hz, 1H), 7.26-7.24 (m, 1H), 7.13 (d, J = 8.8Hz, 1H), 2.08 (s, 3H), 2.04 (s, 3H), 1.78 (s, 6H), 1.66 (s, 6H). LC-MS:m/z 459.1 (M + H)⁺ 396 & 397 XVI.3 Int-I

¹H NMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H), 9.76 (s, 1H), 7.71 (d, J =8.8 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 2.0 Hz, 1H), 7.24(dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 2.11-2.09(m, 1H), 2.07 (s, 3H), 1.62 (s, 2H), 1.45-1.29 (m, 8H), 1.15 (s, 1H),0.83 (s, 6H). LC- MS: m/z 485.1 (M + H)⁺ 342 XVI.4

¹H NMR (400 MHz, DMSO-d6) δ 10.4 (s, 1H), 7.84 (d, J = 8.3 Hz, 1H), 7.78(d, J = 8.3 Hz, 2H), 7.7 (d, J = 8.3 Hz, 2H), 7.56 (t, J = 7.6 Hz, 1H),7.43 (d, J = 8.0 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 3.8 (s, 3H). LC-MS:m/z 371.95 (M + H)⁺².

Intermediate-XVII

Step-a: Synthesis ofN-(4-((3r,5r,7r)-adamantan-1-yl)phenyl)-4-aminobenzenesulfonamide(Intermediate-XVII)

This compound was prepared from Intermediate-XVI (0.85 g, 2 mmol, 1 eq.)by a procedure similar to the one described for Intermediate-I from Ibto afford title product as a white solid (0.75 g, 98%).

¹H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H), 7.38 (d, J=8.8 Hz, 2H), 7.17(d, J=8.8 Hz, 2H), 6.98 (d, J=8.8 Hz, 2H), 6.52 (d, J=8.8 Hz, 2H), 5.93(s, 2H), 2.01 (s, 3H), 1.77 (s, 6H), 1.69 (s, 6H); LC-MS: m/z 383.0(M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-XVII using appropriate reactants and reagents and inpresence of suitable solvents and appropriate reaction conditions.

Inter- mediate CP No. Reactant Structure Analytical data 372 XVII.1XVI.1

LC-MS: m/z 383.1 (M + H)⁺ 392, 393 XVII.2 XVI.2

¹H NMR (400 MHz, DMSO- d6) δ 9.31 (s, 1H), 7.38-7.32 (m, 2H), 7.28 (d, J= 2.0 Hz, 1H), 7.24-7.22 (m, 1H), 7.15 (d, J = 8.8 Hz, 1H), 6.55-6.52(m, 2H), 5.98 (s, 2H), 2.02 (s, 3H), 1.79 (s, 6H), 1.69 (s, 6H). LC-MS:m/z 417.1 (M + H)⁺ 396, 397 XVII.3 XVI.3

¹H NMR (400 MHz, DMSO- d6) δ 9.26 (s, 1H), 7.33 (d, J = 8.4 Hz, 2H),7.27 (s, 1H), 7.22 (d, J = 8.8 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 6.53(d, J = 8.4 Hz, 2H), 5.96 (s, 2H), 2.1 (m, 1H), 1.61 (s, 2H), 1.45-1.29(m, 8H), 1.15 (s, 2H), 0.83 (s, 6H). LC-MS: m/z 445.1 (M + H)⁺

Intermediate-XVIII

Step-a: Synthesis of methyl 2-(4-(N-(4-((3R,5R)-adamantan-1-yl)phenyl)sulfamoyl) phenyl) amino) benzoate (Intermediate-XVIII)

Intermediate-XVIII was prepared from Intermediate-XVII and methyl2-bromobenzoate by a procedure similar to the one described inIntermediate-II.

¹H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 9.31 (s, 1H), 7.89 (d, J=8.4Hz, 1H), 7.63 (d, J=8.4 Hz, 2H), 7.50 (t, J=7.6 Hz, 1H), 7.42 (d, J=8.0Hz, 1H), 7.24-7.19 (m, 4H), 7.03-6.99 (m, 3H), 3.77 (s, 3H), 2.00 (s,3H), 1.76 (s, 6H), 1.69 (s, 6H); LC-MS: m/z 517.1 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-XVIII using appropriate reactants and reagents employingsuitable Pd catalysts and ligands and in presence of suitable solventsand appropriate reaction conditions.

Inter- mediate CP No. Reactant Structure Analytical data 306 XVIII.1Int- XVII

¹H NMR (400 MHz, DMSO- d6) δ 10.33 (s, 1H), 10.05 (s, 1H), 8.48-8.47 (m,1H), 8.31- 8.29 (m, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.69 (d, J = 8.8 Hz,2H), 7.20 (d, J = 8.8 Hz, 2H), 7.03-6.99 (m, 3H), 3.90 (s, 3H), 1.99 (s,3H), 1.76 (s, 6H), 1.68 (s, 6H). LC-MS: m/z 518.0 (M + H)⁺ 312 XVIII.2Int- XVII

¹H NMR (400 MHz, DMSO- d6) δ 9.96 (s, 1H), 9.81 (s, 1H), 7.99 (d, J =8.8 Hz, 2H), 7.79 (t, J = 8.0 Hz, 1H), 7.63 (d, J = 8.8 Hz, 2H), 7.53(d, J = 7.2 Hz, 1H), 7.19 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 8.4 Hz, 1H),7.02 (d, J = 8.4 Hz, 2H), 4.36-4.30 (m, 2H), 1.98 (s, 3H), 1.76 (s, 6H),1.68 (s, 6H), 1.35 (t, J = 6.8 Hz, 3H). LC-MS: m/z 532.2 (M + H)⁺ 342XVIII.3 XVI.4

¹H NMR (400 MHz, DMSO- d6) δ 10.33 (s, 1H), 8.49 (s, 1H), 7.89-8-7.86(m, 1H), 7.58-7.56 (m, 3H), 7.51-7.49 (m, 1H), 7.43 (s, 1H), 7.34- 7.27(m, 2H), 7.16-7.12 (m, 1H), 6.81 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H), 2.05(s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 551.1 (M + H)⁺ 372XVIII.4 XVII.1

LC-MS: m/z 517.2 (M + H)⁺ 392 XVIII.5 XVII.2

¹H NMR (400 MHz, DMSO- d6) δ 9.72 (s, 1H), 9.37 (s, 1H), 7.92 (dd, J₁ =1.6 Hz, J₂ = 8.0 Hz, 1H), 7.61 (d, J = 9.2 Hz, 2H), 7.55-7.51 (m, 1H),7.45 (d, J = 7.6 Hz, 1H), 7.32 (d, J = 2.4 Hz, 1H), 7.27- 7.25 (m, 3H),7.17 (d, J = 8.4 Hz, 1H), 7.04-7.00 (m, 1H), 3.81 (s, 3H), 2.02 (s, 3H),1.80 (d, J = 2.8 Hz, 6H), 1.70 (s, 6H). 393 XVIII.6 XVII.2

¹H NMR (400 MHz, DMSO- d6) δ 10.38 (s, 1H), 9.72 (s, 1H), 8.49 (dd, J₁ =2.0 Hz, J₂ = 4.8 Hz, 1H), 8.31 (dd, J₁ = 2.0 Hz, J₂ = 7.6 Hz, 1H), 7.92(d, J = 8.8 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.30 (d, J = 2.0 Hz, 1H),7.25-7.24 (m, 1H), 7.17 (d, J = 8.4 Hz, 1H), 7.02 (dd, J₁ = 4.8 Hz, J₂ =7.6 Hz, 1H), 3.91 (s, 3H), 2.01 (s, 3H), 1.79 (s, 6H), 1.69 (s, 6H).LC-MS: m/z 552.2 (M + H)⁺ 396 XVIII.7 XVII.3

LC-MS: m/z 577.2 (M + H)⁻ 397 XVIII.8 XVII.3

¹H NMR (400 MHz, DMSO- d6) δ 10.40 (s, 1H), 9.75 (s, 1H), 8.49 (dd, J₁ =2.0 Hz, J₂ = 4.8 Hz, 1H), 8.32 (dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H), 7.93(d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.8 Hz, 2H), 7.29-7.24 (m, 2H), 7.16(d, J = 8.4 Hz, 1H), 7.02 (dd, J₁ = 4.8 Hz, J₂ = 7.6 Hz, 1H), 3.91 (s,3H), 2.10-2.09 (m, 1H), 1.62 (s, 2H), 1.45-1.29 (m, 8H), 1.14 (s, 2H),0.82 (s, 6H). LC-MS: m/z 580.2 (M + H)⁺

Intermediate-XIX

Step-a: Synthesis of phenyl(4-((3r,5r,7r)-adamantan-1-yl)phenyl)carbamate (XIXa)

A solution of Intermediate-I.1 (0.5 g, 2.2 mmol, 1 eq.) and phenylchloroformate (0.42 g, 2.64 mmol, 1.2 eq.) in DCM was added withtriethylamine (0.44 g, 4.4 mmol, 2 eq.) and stirred at RT for 2 h.Reaction mixture was washed with water, concentrated in vacuo andpurified by combi-flash to afford title compound as white solid (0.48 g,630%).

¹H NMR (400 MHz, DMSO-d6) δ10.10 (s, 1H), 7.44-7.39 (m, 4H), 7.31-7.19(m, 5H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H); LC-MS: m/z 348.1(M+H)⁺

Step-b: Synthesis of methyl 2-(4-(3-(4-((3R,5R)-adamantan-1-yl)phenyl)ureido)phenyl) amino) nicotinate (Intermediate-XIX)

Intermediate-XIXa (0.285 g, 0.82 mmol, 1 eq.) and methyl2-((4-aminophenyl)amino) nicotinate (0.2 g, 0.82 mmol, 1 eq.) were takenin THF (20 mL) and added with triethylamine (0.8 mL) and refluxedovernight. Reaction mass was concentrated in vacuo, the obtained crudewas washed with n-hexane twice and dried under vacuum. The crude wastaken further without purification.

¹H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.52 (d, J=14.0 Hz, 2H),8.38-8.37 (m, 1H), 7.76 (d, J=8.4 Hz, 2H), 7.41-7.35 (m, 4H), 7.25 (d,J=8.4 Hz, 2H), 6.84 (dd, J₁=4.4 Hz, J₂=8.0 Hz, 1H), 3.87 (s, 3H), 2.05(s, 3H), 1.84 (s, 6H), 1.73 (s, 6H); LC-MS: m/z 497.2 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-XIX using appropriate reactants and reagents and inpresence of suitable solvents and appropriate reaction conditions.

Inter- mediate CP No. Reactant Structure Analytical data 300 XIX.1VII.14 & Int-I.1

¹H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.45 (d, J = 13.2 Hz, 2H),7.73-7.66 (m, 3H), 7.39-7.34 (m, 5H), 7.25 (d, J = 8.4 Hz, 2H), 6.99 (d,J = 8.4 Hz, 1H), 4.35-4.30 (m, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s,6H), 1.35 (t, J = 7.2 Hz, 3H). LC-MS: m/z 511.1 (M + H)⁺ 307 XIX.2 XI.13& Int-I.1

¹H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.61 (s, 1H), 8.52 (s, 1H),7.88 (d, J = 7.8 Hz, 1H), 7.47 (d, J = 8.3 Hz, 2H), 7.38-7.36 (m, 3H),7.26 (d, J = 8.8 Hz, 2H), 7.18 (d, J = 8.3 Hz, 2H), 7.05 (d, J = 8.3 Hz,1H), 6.75- 6.73 (m, 1H), 3.85 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73(s, 6H). LC-MS: m/z 496.1 (M + H)⁺ 299 XIX.3 XI.17 & Int-I.1

LC-MS: m/z 511.1 (M + H)⁺

Intermediate-XIX.4

Step-a: Synthesis of methyl((4-((4-((3R,5S)-adamantan-1-yl)-2-chlorophenyl) amino)phenyl)carbamoyl) prolinate (XIX.4)

A solution of Intermediate-XI (0.1 g, 0.283 mmol, 1 eq.) in DCM (10 mL)at 0° C. was added with triphosgene (0.084 g, 0.283 mmol, 1 eq.) dropwise and stirred at 0° C. for 1 h. This solution was added to a solutionof methyl prolinate (0.056 g, 0.32 mmol, 1.2 eq.) in DCM (10 mL) andstirred at 0° C. for 1 h. Quenched with sat. bicarbonate solution andextracted with DCM, purified by column chromatography to afford titleproduct as pale brown solid (0.13 g, 90%).

¹H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.34 (d, J=8.8 Hz, 2H), 7.28(d, J=2.0 Hz, 1H), 7.26 (s, 1H), 7.14 (dd, J₁=2.0 Hz, J₂=8.0 Hz, 1H),7.04 (d, J=8.8 Hz, 1H), 6.96 (d, J=9.6 Hz, 2H), 4.37-4.34 (m, 1H), 3.62(s, 3H), 3.56-3.46 (m, 2H), 2.21-2.14 (m, 1H), 2.03 (s, 3H), 1.98-1.84(m, 3H), 1.81 (d, J=2.4 Hz, 6H), 1.71 (s, 6H); LC-MS: m/z 508.4 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-XIX.4 using appropriate reactants and reagents and inpresence of suitable solvents and appropriate reaction conditions.

Inter- mediate CP No. Reactant Structure Analytical data 114 XIX.5Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.34 (d, J = 8.8 Hz, 2H), 7.28(d, J = 2.0 Hz, 1H), 7.26 (s, 1H), 7.14 (dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz,1H), 7.04 (d, J = 8.8 Hz, 1H), 6.96 (d, J = 9.6 Hz, 2H), 4.37- 4.34 (m,1H), 3.62 (s, 3H), 3.56-3.46 (m, 2H), 2.21-2.14 (m, 1H), 2.03 (s, 3H),1.98-1.84 (m, 3H), 1.81 (d, J = 2.4 Hz, 6H), 1.71 (s, 6H). LC-MS: m/z508.2 (M + H)⁺ 134 XIX.6 XI.2

¹H NMR (400 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.47 (s, 1H), 7.41 (d, J = 6.8Hz, 2H), 7.33 (d, J = 1.6 Hz, 1H), 7.28-7.17 (m, 4H), 7.13-7.06 (m, 4H),4.38-4.35 (m, 1H), 3.76 (s, 3H), 3.63-3.48 (m, 2H), 2.27 (s, 3H),2.25-2.17 (m, 1H), 1.96-1.84 (m, 3H). LC-MS: m/z 464.1 (M + H)⁺

Intermediate-XX

Step-a: Synthesis of methyl2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)(methyl) amino) phenyl)(methyl) amino) benzoate (Intermediate-XX)

A solution of intermediate-VI (4 g, 8.85 mmol, 1 eq.) in DMF (80 mL) wascooled to 0° C. and added with sodium hydride (1.06 g, 44.2 mmol, 5 eq.)portion wise and stirred for 15 minutes. Methyl iodide (6.3 g, 44.2mmol, 5 eq.) was added drop wise and the reaction mass was heated at 80°C. for 16 h in a seal tube. Reaction mass was cooled to RT and poured into cold water. The precipitated solid was filtered and dried. This crudewas absorbed over silica and purified by combi-flash to afford titleproduct as pale-yellow solid (3 g, 70.70%).

¹H NMR (400 MHz, DMSO-d6) δ 7.65 (dd, J₁=2.0 Hz, J₂=8.0 Hz, 1H), 7.60(t, J=7.6 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 7.26 (t, J=7.2 Hz, 1H), 7.13(d, J=8.8 Hz, 2H), 6.90 (d, J=8.8 Hz, 2H), 6.67 (d, J=8.8 Hz, 2H), 6.59(d, J=8.8 Hz, 2H), 3.55 (s, 3H), 3.20 (s, 3H), 3.13 (s, 3H), 2.02 (s,3H), 1.80 (s, 6H), 1.71 (s, 6H); LC-MS: m/z 480.25 (M+H)⁺

The below intermediates were prepared by a procedure similar toIntermediate-XX using appropriate reactants and reagents and in presenceof suitable solvents and appropriate reaction conditions.

Intermediate CP No. Reactant Structure Analytical data 198 XX.1 Int-XII

¹H NMR (400 MHz, DMSO-d6) δ 8.31 (dd, J₁ = 2.0 Hz, J₂ = 4.8 Hz, 1H),7.62 (dd, J₁ = 2.0 Hz, J₂ = 7.2 Hz, 1H), 7.49 (d, J = 2.4 Hz, 1H), 7.41(dd, J₁ = 2.4 Hz, J₂ = 8.4 Hz, 1H), 7.26 (d, J = 8.4 Hz, 1H), 6.85-6.80(m, 3H), 6.42 (d, J = 9.2 Hz, 2H), 3.31 (s, 3H), 3.25 (s, 3H), 3.15 (s,3H), 2.07 (s, 3H), 1.89 (s, 6H), 1.74 (s, 6H). 233 XX.2 VI.36

LC-MS: m/z 480.25 (M + H)⁺ 236 XX.3 XII.18

¹H NMR (400 MHz, DMSO-d6) δ 8.31 (dd, J₁ = 2.0 Hz, J₂ = 4.9 Hz, 1H),7.71 (s, 1H), 7.70 (d, J = 1.4 Hz, 1H), 7.39 (d, J = 1.9 Hz, 1H), 7.32(d, J = 2.0 Hz, 2H), 7.04 (d, J = 8.3 Hz, 1H), 6.88-6.85 (m, 1H), 5.28(s, 2H), 3.39 (s, 3H), 3.26 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72(s, 6H). LC-MS: m/z 491.3 (M + H)⁺ 246 XX.4 VI.40

¹H NMR (400 MHz, DMSO-d6) δ 8.35 (d, J = 3.2 Hz, 1H), 7.69 (d, J = 5.6Hz, 1H), 7.25 (d, J = 8.4 Hz, 2H), 6.92-6.86 (m, 7H), 3.37 (s, 3H), 3.31(s, 3H), 3.19 (s, 3H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS:m/z 482.1 (M + H)⁺ 247 XX.5 VI.41

¹H NMR (400 MHz, DMSO-d6) δ 8.37 (dd, J₁ = 1.9 Hz, J₂ = 4.8 Hz, 1H),7.78 (dd, J₁ = 2.0 Hz, J₂ = 7.4 Hz, 1H), 7.25 (d, J = 8.3 Hz, 2H), 7.12(t, J = 7.8 Hz, 1H), 7.00 (d, J = 8.8 Hz, 2H), 6.94-6.90 (m, 1H), 6.56(dd, J₁ = 2.0 Hz, J₂ = 8.3 Hz, 1H), 6.51 (dd, J₁ = 1.5 Hz, J₂ = 7.9 Hz,1H), 6.40 (t, J = 1.9 Hz, 1H), 3.38 (s, 3H), 3.30 (s, 3H), 3.17 (s, 3H),2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 482.1 (M + H)⁺ 260XX.6 Int-XV

LC-MS: m/z 495.2 (M + H)⁺ (Obtained acid directly) 266 XX.7 XII.68

LC-MS: m/z 536.1 (M + H)⁺ (obtained acid directly) 270 XX.8 XII.67

LC-MS: m/z 468.1 (M + H)⁺ 271 XX.9 XII.33

¹H NMR (400 MHz, DMSO-d6) δ 8.52 (dd, J₁ = 1.2 Hz, J₂ = 4.8 Hz, 1H),7.93 (dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H), 7.30 (d, J = 9.2 Hz, 2H), 7.22(d, J = 8.4 Hz, 1H), 7.14-7.11 (m, 3H), 6.44 (d, J = 8.8 Hz, 2H), 3.50(s, 3H), 3.42 (s, 3H), 3.05 (s, 3H), 2.02 (s, 3H), 1.74 (s, 6H), 1.67(s, 6H). LC-MS: m/z 550.1 (M + H)⁺ 273 XX.10 XII.34

¹H NMR (400 MHz, DMSO-d6) δ 7.82-7.78 (m, 1H), 7.42-7.38 (m, 1H),7.46-7.44 (m, 2H), 7.11-7.05 (m, 3H), 6.81-6.78 (m, 2H), 6.38 (d, J =8.8 Hz, 2H), 3.60 (s, 3H), 3.27 (s, 3H), 3.02 (s, 3H), 2.02 (s, 3H),1.79 (s, 6H), 1.70 (s, 6H). LC-MS: m/z 549.1 (M + H)⁺ 275 XX.11 XII.35

¹H NMR (400 MHz, DMSO-d6) δ 7.69 (d, J = 2.8 Hz, 1H), 7.56- 7.52 (m,2H), 7.32 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.0 Hz, 1H), 7.15 (t, J =6.8 Hz, 1H), 7.10 (d, J = 8.8 Hz, 2H), 6.93 (dd, J₁ = 2.8 Hz, J₂ = 9.2Hz, 1H), 6.53 (d, J = 9.2 Hz, 1H), 3.53 (s, 3H), 3.29 (s, 3H), 3.18 (s,3H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 482.25 (M +H)⁺ 276 XX.12 XV.19

¹H NMR (400 MHz, DMSO-d6) δ 7.71 (d, J = 6.4 Hz, 1H), 7.63 (t, J = 7.3Hz, 1H), 7.36 (m, 2H), 7.16 (m, 1H), 7.13 (d, J = 8.8 Hz, 2H), 6.99 (d,J = 8.8 Hz, 2H), 6.62 (m, 4H), 3.57 (s, 3H), 3.28 (m, 4H), 3.25 (s, 3H),3.18 (s, 3H), 1.50 (m, 4H), 1.23 (m, 4H), 0.86 (m, 6H). 277 XX.13 VI.45

LC-MS: m/z 451.1 (M + H)⁺ (obtained acid directly) 286 XX.14 XII.36

¹H NMR (400 MHz, DMSO-d6) δ 7.69 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H),7.64-7.60 (m, 1H), 7.43 (d, J = 2.8 Hz, 1H), 7.36- 7.25 (m, 3H),6.84-6.78 (m, 3H), 6.60 (d, J = 8.8 Hz, 2H), 3.54 (s, 3H), 3.21 (s, 3H),2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 502.1 (M + H)⁺ 296XX.15 VI.49

¹H NMR (400 MHz, DMSO-d6) δ 7.68-7.55 (m, 2H), 7.38-7.05 (m, 4H),6.95-6.83 (m, 2H), 6.75-6.55 (m, 4H), 3.54 (s, 3H), 3.20 (s, 3H), 3.13(s, 3H), 2.10 (m, 1H), 1.62 (s, 2H), 1.46- 1.33 (m, 8H), 1.16 (s, 2H),0.83 (s, 6H). LC-MS: m/z 509.2 (M + H)⁺ 305 XX.16 VI.45

¹H NMR (400 MHz, DMSO-d6) δ 7.67 (d, J = 7.8 Hz, 1H), 7.63- 7.59 (m,1H), 7.35 (d, J = 8.4 Hz, 1H), 7.30-7.26 (m, 1H), 7.10 (t, J = 8.0 Hz,2H), 6.94 (t, J = 8.4 Hz, 4H), 6.73 (d, J = 8.8 Hz, 2H), 6.65-6.60 (m,5H), 3.56-3.53 (m, 5H), 3.21 (s, 3H), 3.17 (s, 3H), 1.53-1.48 (m, 2H),1.33-1.28 (m, 2H), 0.87 (t, J = 6.9 Hz, 3H). LC-MS: m/z 494.1 (M + H)⁺310 XX.17 Int-XV

¹H NMR (400 MHz, DMSO-d6) δ 9.24 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H),7.40-7.38 (m, 1H), 7.28-7.19 (m, 5H), 7.09 (d, J = 8.4 Hz, 2H), 7.02 (d,J = 8.4 Hz, 2H), 6.88 (t, J = 7.2 Hz, 1H), 3.90 (s, 3H), 3.34 (s, 3H),2.02 (s, 3H), 1.81 (s, 6H), 1.70 (s, 6H). LC-MS: m/z 495.1 (M + H)⁺ 314XX.18 XII.40

¹H NMR (400 MHz, DMSO-d6) δ 8.39 (dd, J₁ = 1.4 Hz, J₂ = 4.4 Hz, 1H),7.44 (dd, J₁ = 2.0 Hz, J₂ = 7.9 Hz, 1H), 7.35 (d, J = 8.8 Hz, 2H), 7.03(d, J = 9.3 Hz, 2H), 6.9-6.89 (m, 5H), 3.41 (s, 3H), 3.31 (s, 3H), 2.09(s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 469.3 (M + H)⁺ 325 XX.19XVIII.1

LC-MS: m/z 532.2 (M + H)⁺ 326 XX.20 VI.53

LC-MS: m/z 511.4 (M + H)⁺ 355 XX.21 XX.19

LC-MS: m/z 546.1 (M + H)⁺ 357 XX.22 XIV.16

¹H NMR (400 MHz, DMSO-d6) δ 7.69 (d, J = 8.0 Hz, 1H), 7.65- 7.60 (m,1H), 7.39-7.30 (m, 3H), 7.15-7.07 (m, 3H), 6.94 (d, J = 8.8 Hz, 2H),6.76 (d, J = 8.0 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 3.56 (s, 3H), 3.22(s, 3H), 3.18 (s, 3H), 2.03 (s, 9H), 1.64 (s, 6H). LC-MS: m/z 524.3 (M +H)⁺ 360 XX.23 XII.51

¹H NMR (400 MHz, DMSO-d6) δ 7.71 (d, J = 7.8 Hz, 1H), 7.61 (d, J = 7.4Hz, 1H), 7.43 (d, J = 7.8 Hz, 2H), 7.35-7.30 (m, 3H), 7.21-7.16 (m, 3H),6.94 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.4 Hz, 1H), 6.64 (d, J = 8.8 Hz,2H), 3.56 (s, 3H), 3.22 (s, 3H), 2.94 (m, 1H), 1.13 (d, J = 6.4 Hz, 6H),LC-MS: m/z 486.2 (M + H)⁺ 362 XX.24 XII.52

¹H NMR (400 MHz, DMSO-d6) δ 7.45 (t, J = 8.0 Hz, 1H), 7.13 (t, J = 8.4Hz, 2H), 6.97 (d, J = 8.4 Hz, 1H), 6.91 (d, J = 8.8 Hz, 2H), 6.81 (d, J= 8.0 Hz, 1H), 6.71-6.57 (m, 4H), 3.79 (s, 3H), 3.57 (s, 3H), 3.14 (s,3H), 3.09 (s, 3H), 2.03 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z511.2 (M + H)⁺ 587 XX.25 XII.122

LC-MS: m/z 418.2 (M + H)+

The below compounds were prepared by a procedure similar toIntermediate-VI using appropriate reactants and reagents employingsuitable Pd catalysts and ligands and in presence of suitable solventsand appropriate reaction conditions.

Com- pound No No Reactant Structure Analytical data 51 1

¹H NMR (500 MHz, CDCl₃) δ 9.45 (s, 1H), 8.01 (s, 1H), 7.5-7.7.30 (m,2H), 7.2-7.1 (m, 2H), 6.98 (s, 1H), 6.8 (s, 1H), 6.78-6.26 (m, 4H), 5.99(s, 1H), 3.90 (s, 3H), 2.23- 1.97 (m, 15H) LC-MS: m/z 453.3 (M + H)⁺ 542

LC-MS: m/z 453.1 (M + H)⁺ 57 3

¹H NMR (500 MHz, CDCl₃) δ 9.45 (s, 1H), 8.01 (s, 1H), 7.45-7.23. (d,2H), 7.23-7.01 (m, 6H), 6.98-7.01 (d, 2H), 6.94 (s, 1H), 3.93 (s, 3H),5.99 (s, 1H), 2.21-1.98 (m, 15H) LC-MS: m/z 521.6 (M + H)⁺ 68 4

LC-MS: m/z 481.1 (M + H)⁺ 70 5

LC-MS: m/z 561.2 (M + H)²⁺ 79 6

LC-MS: m/z 515.3 (M + H)⁺ 85 7 Int-XI

¹H NMR (400 MHz, DMSO- d6) δ 8.17 (s, 1H), 7.58 (dd, J₁ = 1.6 Hz, J₂ =8.0 Hz, 1H), 7.44-7.40 (m, 2H), 7.32 (d, J = 2.0 Hz, 1H), 7.20-7.12 (m,2H), 7.09-7.01 (m, 5H), 6.84 (t, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.83 (s,6H), 1.72 (s, 6H). LC-MS: m/z 454.1 (M + H)⁺ 104 8 Int-XI

¹H NMR (400 MHz, DMSO- d6) δ 9.23 (s, 1H), 7.57 (s, 1H), 7.34 (s, 1H),7.2 (d, J = 4.8 Hz, 4H), 7.12 (d, J = 8.8 Hz, 2H), 7.03-6.99 (m, 3H),6.2 (d, J = 8.4 Hz, 1H), 6.05 (d, J = 8.4 Hz, 1H), 2.04 (s, 3H), 1.83(s, 6H), 1.72 (s, 6H). LC-MS: m/z 489.2 (M + H)⁺ 201 9 III.5 & Int-1

¹H NMR (400 MHz, DMSO- d6) δ 8.59 (s, 1H), 7.95 (s, 1H), 7.64 (s, 1H),7.34 (s, 1H), 7.21 (s, 2H), 7.16 (d J = 8.4 Hz, 2H), 6.94 (d, J = 8.4Hz, 2H), 5.28 (s, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS:m/z 350.2 (M + H)⁺; Triazole fragment 225 10 Int-XI

¹H NMR (500 MHz, CDCl₃) δ 8.18-8.17 (m, 1H), 7.49- 7.45 (m, 1H), 7.32(d, J = 1.6 Hz, 1H), 7.28-7.25 (m, 2H), 7.16-7.09 (m, 4H), 6.76 (d, J =8.0 Hz, 1H), 6.72-6.69 (m, 1H), 6.40 (s, 1H), 5.93 (s, 1H), 2.09 (s,3H), 1.87 (s, 6H), 1.80-1.71 (m, 6H). LC- MS: m/z 430.3 (M + H)⁺ 264 11Compound 10

¹H NMR (400 MHz, DMSO- d6) δ 8.71 (d, J = 6.0 Hz, 1H), 8.26 (t, J = 7.2Hz, 1H), 8.05 (s, 1H), 7.63 (t, J = 6.4 Hz, 1H), 7.42 (d, J = 2.0 Hz,1H), 7.37 (d, J = 8.4 Hz, 1H), 7.31- 7.29 (m, 1H), 7.19 (d, J = 8.8 Hz,2H), 7.09 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 1H), 4.96 (t, J =6.8 Hz, 2H), 3.22 (t, J = 7.2 Hz, 2H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73(s, 6H). LC-MS: m/z 484.1 (M)⁺ ion 238 12 XII.28

¹H NMR (400 MHz, DMSO- d6) δ 9.77 (s, 1H), 8.32-8.27 (m, 2H), 7.48-7.39(m, 4H), 7.29 (d, J = 8.3 Hz, 1H), 6.83- 6.76 (m, 1H), 6.52 (d, J = 9.3Hz, 2H), 4.99-4.95 (m, 1H), 4.31 (t, J = 4.9 Hz, 2H), 3.74- 3.71 (m,2H), 3.18 (s, 3H), 2.07 (s, 3H), 1.89 (s, 6H), 1.74 (s, 6H). LC-MS: m/z532.2 (M + H)⁺ 347 13 II.27 & 1.1

¹H NMR (400 MHz, DMSO- d6) δ 7.69 (s, 1H), 7.15 (d, J = 8.8 Hz, 2H),7.10 (d, J = 7.2 Hz, 1H), 7.02-6.96 (m, 5H), 6.90 (d, J = 8.8 Hz, 4H),6.73 (t, J = 7.6 Hz, 1H), 2.19 (s, 3H), 2.03 (s, 3H), 1.82 (s, 6H), 1.72(s, 6H). LC-MS: m/z 409.3 (M + H)⁺ 352 14 XII.48

¹H NMR (400 MHz, DMSO- d6) δ 7.95 (d, J = 16.0 Hz, 1H), 7.86 (s, 1H),7.79 (s, 1H), 7.68 (dd, J₁ = 1.2 Hz, J₂ = 8.0 Hz, 1H), 7.267-7.22 (m,1H), 7.17 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 7.6 Hz, 1H), 6.98 (d, J =9.2 Hz, 2H), 6.94- 6.85 (m, 5H), 6.49 (d, J = 16.0 Hz, 1H), 4.18 (q, J =14.0 Hz, 2H), 2.04 (s, 3H), 1.82 (d, J = 2.34 Hz, 6H), 1.72 (s, 6H),1.25 (t, J = 9.2 Hz, 3H). LC- MS: m/z 493.2 (M + H)⁺ 375 15 XII.56

¹H NMR (400 MHz, DMSO- d6) δ 8.24 (s, 1H), 7.31-7.24 (m, 3H), 7.12-6.94(m, 8H), 6.33 (d, J = 8.0 Hz, 1H), 3.0 (t, J = 6.8 Hz, 2H), 2.68 (t, J =5.6 Hz, 2H), 2.05 (s, 3H), 1.85 (d, J = 2.8 Hz, 6H), 1.70 (s, 6H).LC-MS: m/z 449.3 (M + H)⁺ 354 16 XV.14

¹H NMR (400 MHz, DMSO- d6) δ 9.95 (s, 1H), 9.70 (s, 1H), 8.01 (d, J =8.8 Hz, 2H), 7.92 (d, J = 8.8 Hz, 2H), 7.81- 7.75 (m, 1H), 7.69 (d, J =8.4 Hz, 2H), 7.51 (d, J = 7.6 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H), 7.13(d, J = 8.0 Hz, 1H), 4.36- 4.35 (m, 2H), 2.06 (s, 3H), 1.86 (s, 6H),1.74 (s, 6H), 1.38 (t, J = 7.2 Hz, 3H). LC- MS: m/z 496.2 (M + H)⁺ 38117 Int-XII

¹H NMR (400 MHz, DMSO- d6) δ 9.93 (s, 1H), 8.37 (dd, J₁ = 2.0 Hz, J₂ =4.4 Hz, 1H), 8.22 (dd, J₁ = 2.0 Hz, J₂ = 7.6 Hz, 1H), 7.55 (d, J = 8.8Hz, 2H), 7.41 (s, 1H), 7.31 (d, J = 1.6 Hz, 1H), 7.19-7.12 (m, 2H), 7.04(d, J = 8.8 Hz, 2H), 6.84-6.81 (m, 1H), 3.89 (s, 3H), 2.04 (s, 3H), 1.83(s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.1 (M + H)⁺ 351 18 Int-XI

¹H NMR (400 MHz, DMSO- d6) δ 10.76 (s, 1H), 8.45 (d, J = 7.2 Hz, 1H),8.04 (d, J = 6.8 Hz, 1H), 7.90-7.86 (m, 2H), 7.76 (s, 1H), 7.69 (d, J =8.8 Hz, 2H), 7.37 (s, 1H), 7.28-7.25 (m, 2H), 7.08 (d, J = 8.4 Hz, 2H),2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 518.05 (M + H)⁺ 40619 I.1

¹H NMR (400 MHz, DMSO- d6) δ 10.71 (s, H), 8.01 (d, J = 7.6 Hz, 1H),7.87 (t, J = 8.0 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.51-7.45 (m, 3H),4.00 (s, 3H), 2.07 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 423.2(M + H)⁺ 472 20 XI.16

1H-NMR (400 MHz, CDCl3): δ 9.43 (s, 1H), 8.10 (s, 1H), 7.89 (d, J = 8.8Hz, 1H), 7.33 (d, J = 2 Hz, 1H), 7.27 (d, J = 2 Hz, 2H), 7.16 (d, J =8.4 Hz, 2H), 7.01-6.98 (m, 4H), 6.82 (dd, J1 = 1.6 Hz & J2 = 8.4 Hz,1H), 3.87 (s, 3H), 3.69 (t, J = 5.2 Hz, 2H), 3.41 (s, 3H), 3.30 (s, 3H),2.58 (t, J = 5.6 Hz, 2H), 2.08 (s, 3H), 1.90 (s, 6H), 1.72 (s, 6H).LC-MS: m/z 568.3 (M + H)+. 529 21 XI.25

1H NMR (400 MHz, DMSO-d6): δ 8.68 (s, 1H), 7.55 (d, J = 8.8 Hz, 2H),7.48 (d, J = 2.4 Hz, 1H), 7.32 (dd, J1 = 1.6 & J2 = 8 Hz, 2H), 7.09 (d,J = 5.2 Hz, 1H), 7.05-6.99 (m, 3H), 6.93 (d, J = 8.8 Hz, 2H), 2.36 (d, J= 5.2 Hz, 3H), 2.14 (s, 1H), 1.69 (s, 2H), 1.52-1.35 (m, 8H), 1.18 (s,2H), 0.86 (s, 6H). LC-MS: m/z 424.2 (M + H)+ 531 22 XI.25

1H NMR (400 MHz, DMSO-d6): δ 7.75 (d, J = 4.4 Hz, 2H), 7.51-7.47 (m,2H), 7.34 (dd, J1 = 2 Hz, & J2 = 8.4 Hz, 1H), 7.24 (d, J = 8.4 Hz, 2H),7.14 (d, J = 8 Hz, 1H), 7.05-6.94 (m, 4H), 3.24 (s, 3H), 2.14 (s, 1H),1.69 (s, 2H), 1.53-1.33 (m, 8H), 1.18 (s, 2H), 0.86 (s, 6H). LC-MS: m/z536.2 (M + H)+ 534 23 IX.4

1H NMR (400 MHz, DMSO-d6): δ 8.50 (s, 1H), 8.22 (s, 1H), 8.07 (d, J =8.4 Hz, 1H), 8.02 (s, 1H), 7.77- 7.73 (m, 2H), 7.56 (d, J = 8 Hz, 1H),7.49 (d, J = 1.2 Hz, 1H), 7.37 (dd, J1 = 2 Hz & J2 = 8.4 Hz, 1H), 7.21(d, J = 8 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 2.41 (d, J = 4.8 Hz, 3H),2.06 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H), LC-MS: m/z 525.2 (M + H)+. 60824 XI.32

1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.44 (d, J = 8.8 Hz, 2H),7.33- 7.31 (m, 2H), 7.21 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 7.10 (dd,J1 = 2.0 Hz, J2 = 6.4 Hz, 2H), 6.99 (dd, J1 = 2.4 Hz, J2 = 6.8 Hz, 2H),6.76 (d, J = 8.8 Hz, 2H), 3.78 (s, 3H), 3.25 (s, 3H). LC-MS: m/z 398.1(M + H)+. 629 25 XI.53

1H NMR (400 MHz, DMSO-d6) δ 7.11-7.07 (m, 4H), 6.87 (s, 1H), 6.83 (d, J= 8.8 Hz, 2H), 6.77 (d, J = 2.4 Hz, 2H), 6.71 (d, J = 8.4 Hz, 1H), 6.53(s, 1H), 3.75 (s, 3H), 3.18 (s, 3H), 2.05 (s, 3H), 2.49-2.48 (m, 1H),1.77-1.76 (m, 5H), 1.37-1.32 (m, 5H). LC-MS: m/z 469.3 (M + H)+. 657 26XI.53

1H NMR (400 MHz, DMSO-d6) δ 8.55 (s, 1H), 7.84 (d, J = 2.0 Hz, 1H), 7.64(dd, J1 = 2.0 Hz, J2 = 9.6 Hz, 1H), 7.25 (d, J = 4.8 Hz, 1H), 7.18 (d, J= 8.4 Hz, 2H), 7.03 (d, J = 8.0 Hz, 3H), 6.86 (d, J = 2.0 Hz, 1H), 6.74(dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H), 6.49 (d, J = 8.8 Hz, 1H), 3.24 (s,3H), 2.46-2.43 (m, 1H), 2.38 (d, J = 4.8 Hz, 3H), 2.06 (s, 3H),1.80-1.68 (m, 5H), 1.40-1.29 (m, 5H). LC-MS: m/z 489.2 (M + H)+. 688 27VII

1H NMR (400 MHz, DMSO-d6) δ 9.35 (s, 1H), 7.70-7.66 (m, 1H), 7.50-7.48(m, 2H), 7.38 (s, 1H), 7.31- 7.26 (m, 2H), 7.18-7.15 (m, 1H), 7.21-7.10(m, 1H), 7.06-7.02 (m, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H).LC-MS: m/z 455.20 (M + H)+ 694 28 VII

1H NMR (400 MHz, DMSO-d6) δ 9.32 (s, 1H), 7.72 (t, J = 7.6 Hz, 1H), 7.62(d, J = 8.4 Hz, 2H), 7.43-7.42 (m, 1H), 7.32-7.30 (m, 2H), 7.17 (d, J =7.2 Hz, 2H), 7.09 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 8.8 Hz, 2H), 6.94(d, J = 8.0 Hz, 1H), 2.60 (d, J = 4.4 Hz, 3H), 2.04 (s, 3H), 1.83 (s,6H), 1.72 (s, 6H). LC-MS: m/z m/z 523.2 (M + H)+

The below compounds were prepared by a procedure similar toIntermediate-XIII using appropriate reactants and reagents and inpresence of suitable solvents and appropriate reaction conditions.

Compound CP No Reactant Structure Analytical data 86 29 Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 7.20 (d, J = 2.0 Hz, 1H), 7.03 (dd, J₁ = 1.6Hz, J₂ = 8.0 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.71 (d, J= 8.8 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 5.28 (d, J = 8.4 Hz, 1H),4.03-4.00 (m, 1H), 3.89-3.81 (m, 2H), 3.11-3.06 (m, 1H), 2.02-1.90 (m,5H), 1.88-1.78 (m, 8H), 1.73-1.61 (m, 7H), 1.56-1.49 (m, 1H), 0.96 (t, J= 7.2 Hz, 3H). LC-MS: m/z (M + H)+ 87 30 Int-XI

¹H NMR (400 MHz, DMSO-d6) δ (d, J = 2.0 Hz, 1H), 7.03 (dd, J₁ = 1.6 Hz,J₂ = 8.0 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.83 (s, 1H), 6.71 (d, J =8.8 Hz, 1H), 6.53 (d, J = 8.8 Hz, 2H), 5.55-5.50 (m, 1H), 4.05-4.03 (m,2H), 3.97-3.91 (m, 1H), 2.69-2.61 (m, 1H), 2.02-1.95 (m, 5H), 1.79 (s,6H), 1.78-1.68 (m, 9H), 1.54-1.45 (m, 1H), 1.15 (t, J = 7.2 Hz, 3H).LC-MS: m/z 493.2 (M + H)⁺ 516 31 Compound 257

1H-NMR (400 MHz, DMSO-d6): 7.14- 7.02 (m, 5H), 6.91 (d, J = 8.8 Hz, 2H),6.79-6.76 (m, 1H), 6.71-6.50 (m, 4H), 5.21-5.17 (m, 1H), 4.46 (d, J = 7Hz, 2H), 3.74 (s, 3H), 3.13 (s, 3H), 2.03 (s, 3H), 1.81-1.79 (m, 6H),1.72-1.70 (m, 6H). LC-MS: m/z 469.3 (M + H)+.

The below compound was prepared by a procedure similar toIntermediate-XI using appropriate reactants and reagents and in presenceof suitable solvents and appropriate reaction conditions.

Compound CP No Reactant Structure Analytical data 231 32 XII.69

¹H NMR (400 MHz, DMSO-d6) δ 7.60 (s, 1H), 7.55 (d, J = 8.8 Hz, 2H), 7.46(dd, J₁ = 1.2 Hz, J₂ = 4.8 Hz, 1H), 7.27 (d, J = 2.0 Hz, 1H), 7.15-7.11(m, 2H), 7.02-7.00 (m, 3H), 6.87-6.85 (m, 1H), 6.58- 6.56 (m, 1H), 5.00(s, 2H), 2.03 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 445.2 (M +H)⁺

The below compound was prepared by a procedure similar toIntermediate-XIX using appropriate reactants and reagents and inpresence of suitable solvents and appropriate reaction conditions.

Compound CP No Reactant Structure Analytical data 82 33 I.1

¹H NMR (400 MHz, DMSO-d6) δ 8.20 (s, 1H), 7.38 (d, J = 8.8 Hz, 2H), 7.20(d, J = 8.8 Hz, 2H), 4.37-4.34 (m, 1H), 3.60 (s, 3H), 3.56-3.45 (m, 2H),2.20-2.16 (m, 1H), 2.03 (s, 3H), 1.96-1.92 (m, 3H), 1.83 (d, J = 2.0 Hz,6H), 1.72 (s, 6H). LC-MS: m/z 383.1 (M + H)⁺

Synthesis of 2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)amino)phenyl)amino)benzoic acid (Compound-24 (CP-55))

To a solution of Intermediate-VI (8.5 g, 16.5 mmol, 1 eq.) inTHF:MeOH:H₂O (40+40+20 mL) LiOH×H₂O (3.3 g, 82.4 mmol, 5 eq.) was addedand stirred at RT for 16 h. Reaction mass was concentrated in vacuo,diluted with water and acidified with 2 N HCl to pH 5. The precipitateobtained was filtered and dried under vacuum. This solid was washed with10% ether in hexane mixture and dried to afford title product asoff-white solid (5.5 g, 670).

¹H NM/R (400 MHz, DMSO-d6) δ 12.99 (s, 1H), 9.42 (s, 1H), 8.00 (s, 1H),7.85 (d, J=6.8 Hz, 1H), 7.32 (t, 1H), 7.21 (d, J=8.8 Hz, 2H), 7.11-6.96(m, 7H), 6.67 (t, J=3.4 Hz, 1H), 2.08 (s, 3H), 1.83 (s, 6H), 1.72 (s,6H); LC-MS: m/z 438.4 (M+H)⁺

The below compounds were prepared by a procedure similar to the onedescribed in compound-24 by using appropriate reagents in the presenceof suitable solvents at appropriate reaction conditions. Thephysiochemical characteristics of the compounds are also summarized.

Com- pound Reac- CP No tant Structure Analytical data 52 25

LC-MS: m/z 439.1 (M + H)⁺ 58 26

LC-MS: m/z 507.2 (M + H)⁺ 59 27

LC-MS: m/z 506.2 (M − H)⁻ 60 28

LC-MS: m/z 521.2 (M + H)⁺ 61 29

LC-MS: m/z 575.2 (M + H)⁺ 62 30

LC-MS: m/z 457.2 (M + H)⁺ 64 31 VI.1

¹H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 9.48 (s, 1H), 7.86 (d, J =7.3 Hz, 1H), 7.52 (s, 1H), 7.33 (t, J = 7.4 Hz, 2H), 7.20 (s, 2H), 7.13(d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 7.01 (s, 1H), 6.68 (t, J= 7.4 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z472.1 (M + H)⁺ 65 32

LC-MS: m/z 454.1 (M + H)⁺ 66 33

LC-MS: m/z 539.1 (M − H)⁻ 67 34

MLC-MS: m/z 440.2 (M + H)⁺ 69 35 Int-XV

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 10.02 (s, 1H), 9.81 (s, 1H),7.97-7.94 (m, 3H), 7.69 (d, J = 8.8 Hz, 2H), 7.51-7.43 (m, 2H),7.35-7.31 (m, 4H), 6.93- 6.89 (m, 1H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74(s, 6H). LC-MS: m/z 467.1 (M + H)⁺ 71 36

LC-MS: m/z 545.1 (M)⁺ 80 37

LC-MS: m/z 501.1 (M − H)⁺ 83 38 Com- pound 23

¹H NMR (400 MHz, DMSO-d6) δ 12.36 (s, 1H), 8.16 (s, 1H), 7.38 (d, J =8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 4.31- 4.28 (m, 1H), 3.54-3.50 (m,1H), 3.46-3.40 (m, 1H), 2.16-2.14 (m, 1H), 2.03 (s, 3H), 1.95-1.85 (m,3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 369.1 (M + H)⁺ 88 39 Com-pound 20

¹H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.4 Hz, 1H), 7.03 (d, J = 1.6Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H), 6.83 (s, 1H), 6.75 (d, J = 8.8 Hz,1H), 6.61 (d, J = 8.8 Hz, 2H), 3.96-3.90 (m, 1H), 2.99- 2.93 (m, 1H),2.02-1.79 (m, 6H), 1.78-1.69 (m, 7H), 1.70-1.62 (m, 7H), 1.59-1.51 (m,1H). LC-MS: m/z 465.2 (M + H)⁺ 89 40 Com- pound 21

¹H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.4 Hz, 1H), 7.06 (dd, J₁ = 2.0Hz, J₂ = 8.8 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 8.0 Hz,1H), 6.56 (d, J = 8.8 Hz, 2H), 3.93-3.91 (m, 1H), 2.61-2.59 (m, 1H),2.02- 1.97 (m, 5H), 1.78 (s, 6H), 1.75-1.66 (m, 9H), 1.52-1.44 (m, 1H).LC-MS: m/z 465.1 (M + H)⁺ 93 41 VI.2

¹H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.52 (s, 1H), 7.88 (dd, J₁ =1.5 Hz, J₂ = 8.3 Hz, 1H), 7.69 (s, 1H), 7.42-7.30 (m, 4H), 7.25 (dd, J₁= 8.3 Hz, J₂ = 12.7 Hz, 1H), 7.21-7.07 (m, 8H), 6.71 (t, J = 7.3 Hz,1H), 3.06-3.02 (m, 1H), 1.14 (d, J = 6.8 Hz, 6H). LC-MS: m/z 457.1 (M +H)⁺ 98 42 Isomer- 1 of com- pound 41

¹H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 4.0 Hz, 1H), 7.04 (dd, J₁ = 2.0Hz, J₂ = 8.4 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.74 (d, J= 8.8 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 3.93- 3.89 (m, 1H), 2.95-2.92(m, 1H), 2.02 (s, 3H), 1.99-1.93 (m, 1H), 1.88- 1.78 (m, 8H), 1.74-1.63(m, 7H), 1.57-1.50 (m, 1H), 1.35-1.33 (m, 1H). LC-MS: m/z 465.2 (M + H)⁺99 43 Isomer- 2 of com- pound 41

¹H NMR (400 MHz, DMSO-d6) δ 7.20 (d, J = 2.0 Hz, 1H), 7.04 (d, J = 8.8Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.75 (d, J = 8.8 Hz,1H), 6.60 (d, J = 8.8 Hz, 2H), 3.93-3.89 (m, 1H), 2.95-2.92 (m, 1H),2.02 (s, 3H), 1.99-1.92 (m, 1H), 1.88-1.78 (m, 8H), 1.74-1.63 (m, 7H),1.57- 1.50 (m, 1H), 1.35-1.33 (m, 1H). LC-MS: m/z 465.2 (M + H)⁺ 100 44Isomer- 1 of com- pound 42

¹H NMR (400 MHz, DMSO-d6) δ 12.15 (bs, 1H), 7.21 (d, J = 2.4 Hz, 1H),7.04 (dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.83(s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 6.55 (d, J = 8.8 Hz, 2H), 5.50 (bs,1H), 3.92 (m, 1H), 2.67-2.57 (m, 1H), 2.02 (s, 3H), 1.99- 1.93 (m, 2H),1.79 (s, 6H), 1.75-1.68 (m, 9H), 1.50-1.44 (m, 1H). LC- MS: m/z 46.52(M + H)⁺ 101 45 Isomer- 2 of com- pound 42

¹H NMR (400 MHz, DMSO-d6) δ 12.18 (bs, 1H), 7.21 (d, J = 2.0 Hz, 1H),7.04 (dd, J₁ = 1.6 Hz, J₂ = 8.8 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.83(s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 6.55 (d, J = 8.8 Hz, 2H), 5.50 (bs,1H), 3.93- 3.91 (m, 1H), 2.67-2.57 (m, 1H), 2.02-1.94 (m, 5H), 1.78 (s,6H), 1.77- 1.68 (m, 8H), 1.49-1.46 (m, 1H). LC-MS: m/z 465.2 (M + H)⁺102 46 XIII.1

¹H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.0 Hz, 1H), 7.04 (dd, J₁ = 2.4Hz, J₂ = 8.8 Hz, 1H), 6.89 (s, 1H), 6.87 (s, 2H), 6.77 (d, J = 8.0 Hz,1H), 6.66 (d, J = 8.8 Hz, 2H), 3.87 (s, 1H), 2.62 (m, 1H), 2.02 (s, 3H),1.91-1.78 (m, 8H), 1.70 (s, 6H), 1.68- 1.42 (m, 4H), 1.41-1.25 (m, 2H).LC-MS: m/z 479.2 (M + H)⁺ 103 47 XIII.1

¹H NMR (400 MHz, DMSO-d6) δ 12.00 (bs, 1H), 7.20 (d, J = 2.0 Hz, 1H),7.03 (d, J = 6.8 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.75(d, J = 8.8 Hz, 1H), 6.57 (d, J = 8.0 Hz, 2H), 5.20 (bs, 1H), 3.40-3.36(m, 1H), 2.22-2.01 (m, 1H), 2.02 (s, 3H), 1.82-1.78 (m, 2H), 1.78 (s,6H), 1.70-1.65 (m, 9H), 1.51- 1.42 (m, 1H), 1.38-1.29 (m, 1H), 1.09-1.02(m, 1H), LC-MS: m/z 479.2 (M + H)⁺ 106 48 XV.2

¹H NMR (400 MHz, DMSO-d6) δ 12.4 (bs, 1H), 8.01 (bs, 1H), 7.44- 7.40 (m,3H), 7.33-7.27 (m, 2H), 6.91 (d, J = 8.3 Hz, 2H), 4.37 (m, 1H), 3.58(bs, 2H), 2.25-2.22 (m, 1H), 2.05 (s, 3H), 1.85 (s, 9H), 1.73 (s, 6H).LC-MS: m/z 479.2 (M + H)⁺ 107 49 XV.3

¹H NMR (400 MHz, DMSO-d6) δ 12.4 (bs, 1H), 7.99 (bs, 1H), 7.42- 7.38 (m,3H), 7.31-7.25 (m, 2H), 6.89 (d, J = 8.3 Hz, 2H), 4.35 (m, 1H), 3.56 (m,2H), 2.23-2.20 (m, 1H), 2.03 (s, 3H), 1.83 (s, 9H), 1.71 (s, 6H). LC-MS:m/z 479.2 (M + H)⁺ 108 50 XIX.4

¹H NMR (400 MHz, DMSO-d6) δ 12.36 (s, 1H), 8.13 (s, 1H), 7.35 (d, J =8.8 Hz, 2H), 7.28 (d, J = 2.4 Hz, 1H), 7.25 (s, 1H), 7.14 (dd, J₁ = 2.0Hz, J₂ = 8.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.96 (d, J = 8.8 Hz,2H), 4.31- 4.29 (m, 1H), 3.56-3.42 (m, 2H), 2.18-2.12 (m, 1H), 2.03 (s,3H), 1.95- 1.84 (m, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC- MS: m/z 494.2(M + H)⁺ 113 51 VI.3

¹H NMR (400 MHz, DMSO-d6) δ 12.96 (s, 1H), 9.52 (s, 1H), 7.88 (dd, J₁ =1.5 Hz, J₂ = 7.8 Hz, 1H), 7.7 (s, 1H), 7.38-7.34 (m, 2H), 7.30- 7.16 (m,10H), 7.08 (d, J = 8.3 Hz, 1H), 6.71 (t, J = 7.3 Hz, 1H), 2.27 (s, 3H).LC-MS: m/z 429.1 (M + H)⁺ 114 52 XIX.5

¹H NMR (400 MHz, DMSO-d6) δ 12.36 (s, 1H), 8.13 (s, 1H), 7.35 (d, J =8.8 Hz, 2H), 7.28 (d, J = 2.4 Hz, 1H), 7.25 (s, 1H), 7.14 (dd, J₁ = 2.0Hz, J₂ = 8.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.96 (d, J = 8.8 Hz,2H), 4.31- 4.29 (m, 1H), 3.56-3.42 (m, 2H), 2.18-2.12 (m, 1H), 2.03 (s,3H), 1.95- 1.84 (m, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC- MS: m/z 492.4(M + H)⁻ 115 53 VI.4

¹H NMR (400 MHz, DMSO-d6) δ 13.00 (s, 1H), 9.52 (s, 1H), 7.88 (d, J =7.9 Hz, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.75- 7.69 (m, 2H), 7.60 (t, J =7.8 Hz, 1H), 7.44 (d, J = 7.2 Hz, 1H), 7.38-7.25 (m, 2H), 7.23-7.18 (m,5H), 7.14-7.09 (m, 2H), 6.72 (t, J = 8.0 Hz, 1H). LC-MS: m/z 483.1 (M +H)⁺ 116 54 VI.5

¹H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.49 (s, 1H), 8.32 (s, 1H),8.87 (dd, J₁ = 7.8 Hz, J₂ = 7.8 Hz, 1H), 7.88 (d, J = 1.4 Hz, 1H), 7.51(dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 1H), 7.43 (dd, J₁ = 6.4 Hz, J2 = 8.8 Hz,4H), 7.19- 7.14 (m, 4H), 7.10 (d, J = 8.3 Hz, 2H), 7.04 (d, J = 8.3 Hz,1H), 6.70 (t, J = 7.9 Hz, 1H). LC-MS: m/z 433.1 (M + H)⁺ 117 55 VI.5

¹H NMR (400 MHz, DMSO- d6) δ 12.93 (s, 1H), 9.47 (s, 1H), 8.28 (s, 1H),7.87 (d, J = 9.3 Hz, 1H), 7.64 (dd, J₁ = 5.4 Hz, J₂ = 8.3 Hz, 2H), 7.52(d, J = 8.3 Hz, 2H), 7.33 (t, J = 7.4 Hz, 1H), 7.24 (t, J = 8.8 Hz, 2H),7.14 (m, 6H), 7.03 (d, J = 8.3 Hz, 1H), 6.70 (t, J = 7.3 Hz, 1H). LC-MS:m/z (M + H)⁺ 118 56 VI.6

¹H NMR (400 MHz, DMSO-d6) δ 12.96 (s, 1H), 9.51 (s, 1H), 7.88 (d, J1 =1.5 Hz, J2 = 8.3 Hz, 1H), 7.69 (s, 1H), 7.53 (d, J = 2.0 Hz, 1H),7.38-7.29 (m, 4H), 7.24- 7.15 (m, 5H), 7.09 (t, J = 8.4 Hz, 2H), 7.01(t, J = 7.4 Hz, 1H), 6.71 (t, J = 7.8 Hz, 1H), 3.79 (s, 3H). LC-MS: m/z445.1 (M + H)⁺ 121 57 VI.7

¹H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 9.53 (s, 1H), 7.89 (d, J =1.0 Hz, 1H), 7.66 (s, 1H), 7.37-7.23 (m, 2H), 7.21-7.14 (m, 5H),7.13-7.06 (m, 4H), 6.97 (dd, J₁ = 1.4 Hz, J₂ = 8.3 Hz, 1H), 6.71 (t, J =7.3 Hz, 1H), 2.03 (s, 6H). LC-MS: m/z 442.4 (M + H)⁺ 122 58 VI.8

¹H NMR (400 MHz, DMSO-d6) δ 12.98 (s, 1H), 9.54 (s, 1H), 7.88 (dd, J₁ =0.9 Hz, J₂ = 7.8 Hz, 1H), 7.77 (s, 1H), 7.55 (dd, J₁ = 6.8 Hz, J₂ = 8.3Hz, 1H), 7.48 (d, J = 1.5 Hz, 1H), 7.44-7.35 (m, 4H), 7.28-7.25 (m, 2H),7.23-7.19 (m, 4H), 7.10 (d, J = 8.3 Hz, 1H), 6.72 (t, J = 7.3 Hz, 1H).LC-MS: m/z 449 (M + H)⁺ 124 59 Int-XII

¹H NMR (400 MHz, DMSO-d6) δ 12.18 (bs, 1H), 8.16-8.13 (m, 2H), 7.62 (d,J = 8.8 Hz, 2H), 7.27 (d, J = 2.0 Hz, 1H), ¹H NMR (400 MHz, DMSO-d6) δ7.22 (s, 1H), 7.13 (dd, J₁ = 2.4 Hz, J₂ = 8.4 Hz, 1H), 7.04- 7.02 (m,3H), 6.66 (dd, J₁ = 4.8 Hz, J₂ = 7.2 Hz, 1H), 2.03 (s, 3H), 1.82 (s,6H), 1.71 (s, 6H). LC-MS: m/z 474 (M + H)⁺ 125 60 VI.9

¹H NMR (400 MHz, DMSO-d6) δ 13.61 (s, 1H), 10.6 (s, 1H), 8.5 (d, J = 8.8Hz, 1H), 8.4 (dd, J₁ = 2.0 Hz, J₂ = 4.8 Hz, 1H), 8.28 (dd, J₁ = 2.0 Hz,J₂ = 8.0 Hz, 1H), 7.4 (d, J = 2.0 Hz, 1H), 7.32 (dd, J₁ = 2.0 Hz, J₂ =8.8 Hz, 1H), 6.92 (dd, J₁ = 4.4 Hz J₂ = 7.2 Hz, 1H), 2.06 (s, 3H), 1.86(d, J = 2.8 Hz, 6H), 1.7 (s, 6H). LC-MS: m/z 383.0 (M + H)⁺ 126 611VI.10

¹H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.52 (bs, 1H), 7.87 (dd, J₁= 1.5 Hz, J₂ = 7.8 Hz, 1H), 7.59 (s, 1H), 7.35- 7.05 (m, 12H), 6.71 (t,J = 6.9 Hz, 1H), 2.05 (s, 3H), 1.90 (s, 3H). LC-MS: m/z 443.1(M + H)⁺127 62 VI.65

¹H NMR (400 MHz, DMSO-d6) δ 13.45 (s, 1H), 10.79 (s, 1H), 8.55 (s, 1H),8.49 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 6.0 Hz, 1H), 7.94 (d, J = 7.2 Hz,1H), 7.66 (d, J = 8.4 Hz, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.37-7.32 (m,2H), 7.02 (t, J = 7.2 Hz, 1H), 6.29 (d, J = 5.2 Hz, 1H), 2.08 (s, 3H),1.89 (s, 6H), 1.75 (s, 6H). LC-MS: m/z 475.1 (M + H)⁺ 128 63 XIII.2

¹H NMR (400 MHz, DMSO-d6) δ 11.9 (bs, 1H), 7.64 (s, 1H), 7.36 (s, 1H),7.26-7.23 (m, 2H), 6.47 (bs, 1H), 6.40 (d, J = 9.3 Hz, 2H), 6.10 (bs,1H), 3.91 (m, 1H), 2.94 (m, 1H), 2.05 (bs, 3H), 1.94 (m, 2H), 1.84 (s,6H), 1.80-1.63 (m, 8H), 1.55-1.50 (m, 2H). LC-MS: m/z 533.2 (M + H)⁺ 12964 XIII.2

¹H NMR (400 MHz, DMSO-d6) δ 12.18 (s, 1H), 7.69 (s, 1H), 7.37 (s, 1H),7.26 (s, 2H), 7.41- 7.38 (m, 2H), 6.30 (s, 1H), 6.08 (d, J = 6.8 Hz,1H), 3.92-3.89 (m, 1H), 2.05 (s, 3H), 2.02-1.91 (m, 2H), 1.85 (s, 6H),1.73 (s, 6H), 1.70-1.60 (m, 2H), 1.52-1.38 (m, 3H). LC-MS: m/z 533.2(M + H)⁺ 130 65 XIII.3

¹H NMR (400 MHz, DMSO-d6) δ 7.0 (d, J = 8.0 Hz, 2H), 6.53 (d, J = 8.4Hz, 2H), 3.93-3.88 (m, 1H), 2.94-2.64 (m, 1H), 1.99 (bs, 5H), 1.95- 1.77(m, 2H), 1.75 (bs, 7H), 1.72-1.54 (bs, 7H). LC-MS: m/z 340.1 (M + H)⁺131 66 XIII.4

¹H NMR (400 MHz, DMSO-d6) δ 7.02 (d, J = 8.8 Hz, 2H), 6.55 (d, J = 8.4Hz, 2H), 3.74 (bs, 1H), 2.08 (bs, 3H), 2.01- 1.88 (m, 1H), 1.77-1.73(bs, 6H), 1.70 (bs, 8H), 1.53-1.47 (m, 4H), 1.37- 1.27 (m, 2H). LC-MS:m/z 354.1 (M + H)⁺ 134 67 XIX.6

¹H NMR (400 MHz, DMSO-d6) δ 12.37 (bs, 1H), 8.21 (bs, 1H), 7.46- 7.41(m, 3H), 7.39 (s, 1H), 7.33-7.17 (m, 4H), 7.13-7.06 (m, 4H), 4.3 (d, J =6.4 Hz, 1H), 3.55-3.47 (m, 2H), 2.25 (s, 3H), 2.19-2.13 (m, 1H), 1.96-1.88 (m, 3H). LC-MS: m/z 450.1 (M + H)⁺ 135 68 VI.11

¹H NMR (400 MHz, DMSO-d6) δ 12.30- 10.99 (bs, 1H), 8.20 (s, 1H),8.00-7.91 (m, 4H), 7.63 (d, J = 8.8 Hz, 2H), 7.55-7.48 (m, 4H), 7.33-7.23 (m, 3H), 6.75 (t, J = 7.6 Hz, 1H). LC-MS: m/z 373.3 (M + H)⁺ 136 69XIII.5

¹H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.0 Hz, 1H), 7.05 (dd, J₁ = 2.0Hz, J₂ = 10.8 Hz, 1H), 6.88 (d, J = 8.4 Hz, 2H), 6.83 (s, 1H), 6.76 (d,J = 8.8 Hz, 1H), 6.58 (d, J = 8.4 Hz, 2H), 3.8 (s, 1H), 2.03 (s, 3H),1.90- 1.83 (m, 1H), 1.80-1.65 (m, 17H), 1.64-1.56 (m, 3H), 1.52-1.41 (m,3H). LC-MS: m/z 507.3 (M + H)⁺ 138 70 Int-XIII

¹H NMR (400 MHz, DMSO-d6) δ 12.53 (bs, 1H), 8.81 (s, 1H), 7.79 (d, J =8.0 Hz, 1H), 7.36- 7.32 (m, 1H), 7.18 (d, J = 2.0 Hz, 1H), 7.12 (d, J =8.8 Hz, 1H), 6.79-6.74 (m, 2H), 6.52 (d, J = 7.2 Hz, 1H), 4.51 (d, J =7.2 Hz, 1H), 3.7 (s, 1H), 3.48 (s, 1H), 2.02 (s, 3H), 1.78- 1.7 (m,18H), 1.58-1.55 (m, 2H). LC-MS: m/z 479.3 (M + H)⁺ 139 71 Int-XIII

¹H NMR (400 MHz, DMSO-d6) δ 12.53 (s, 1H), 7.78-7.76 (m, 2H), 7.34 (t, J= 8.0 Hz, 1H), 7.17 (d, J = 2.0 Hz, 1H), 7.11 (dd, J₁ = 1.2 Hz, J₂ = 8.0Hz, 1H), 6.78-6.73 (m, 2H), 6.54-6.50 (m, 1H), 4.5 (d, J = 8.4 Hz, 1H),3.4- 3.35 (m, 2H), 2.08-1.98 (m, 7H), 1.78 (s, 6H), 1.7 (s, 6H),1.47-1.23 (m, 4H). LC- MS: m/z 479.4 (M + H)⁺ 140 72 VI.12

¹H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.49 (bs, 1H), 7.86 (dd, J₁= 1.5 Hz, J₂ = 7.9 Hz, 1H), 7.42 (s, 1H), 7.37 (s, 1H), 7.34 (m, 1H),7.28-7.25 (m, 1H), 7.18-7.04 (m, 6H), 6.70 (t, J = 7.4 Hz, 1H), 5.91 (s,1H), 2.38-2.32 (m, 2H), 1.91-1.89 (m, 2H), 1.77- 1.74 (m, 2H), 1.05 (m,6H). LC-MS: m/z 446.3 (M + H)⁺ 141 73 VI.13

¹H NMR (400 MHz, DMSO-d6) δ 13.00-12.8 (bs, 1H), 8.34 (s, 2H), 7.90-7.82(m, 2H), 7.32 (d, J = 10.0 Hz, 2H), 7.26- 7.13 (m, 3H), 6.96 (bs, 1H),1.98 (s, 3H), 1.83 (d, J = 2.4 Hz, 6H), 1.72 (s, 6H), 1.33 (s, 9H). LC-MS: m/z 575.1 (M + H)⁺ 142 74 VI.14

¹H NMR (400 MHz, DMSO-d6) δ 12.91 (bs, 1H), 8.77 (s, 1H), 8.30 (s, 1H),8.05 (s, 1H), 7.89- 7.86 (m, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.55-7.51(m, 1H), 7.38-7.37 (m, 2H), 7.27 (t, J = 2.0 Hz, 2H), 2.05 (s, 3H), 1.85(s, 6H), 1.73 (s, 6H), 1.33 (s, 9H). LC-MS: m/z 575.1 (M + H)⁺ 143 75Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 13.40- 13.00 (bs, 1H), 8.66 (s, 1H), 8.09(d, J = 2.0 Hz, 1H), 7.76 (s, 1H), 7.37 (d, J = 1.2 Hz, 1H), 7.28- 7.22(m, 2H), 7.17 (d, J = 7.6 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.89 (d, J= 6.8 Hz, 1H), 2.05 (s, 3H), 1.89-1.84 9bs, 6H), 1.73 (s, 6H). LC-MS:m/z 474.1 (M + H)⁺ 144 76 VI.15

¹H NMR (400 MHz, DMSO-d6) δ 12.86 (bs, 1H), 7.97 (d, J = 2.8 Hz, 1H),7.86 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H), 7.77 (s, 1H), 7.54-7.48 (m,2H), 7.41-7.33 (m, 3H), 7.21 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz,1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.32 (s, 9H). LC- MS: m/z574.1 (M + H)⁺ 145 77 XV.5

¹H NMR (400 MHz, DMSO-d6) δ 11.93 (bs, 1H), 7.99 (s, 1H), 7.83 (bs, 1H),7.66 (d, J = 8.8 Hz, 2H), 7.40 (s, 1H), 7.29-7.26 (m, 2H), 6.90 (d, J =8.8 Hz, 2H), 4.54- 4.50 (m, 1H), 2.92-2.90 (m, 1H), 2.08 (bs, 3H), 2.05(m, 2H), 1.85 (s, 6H), 1.83-1.80 (m, 2H), 1.73 (s, 6H), 1.52-1.49 (m,2H). LC-MS: m/z (M + H)⁺ 146 78 XII.9

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.7 (s, 1H), 7.9 (dd, J₁ = 1.6Hz, J₂ = 8.0 Hz, 1H), 7.52-7.39 (m, 5H), 7.34-7.24 (m, 5H), 7.16- 7.13(m, 3H), 6.82 (t, J = 8.0 Hz, 1H). LC-MS: m/z 356.0 (M + H)⁺ 148 79

LC-MS: m/z 467.3 (M + H)⁺ 149 80

LC-MS: m/z 507.2 (M + H)⁺ 151 81

LC-MS: m/z 438.2 (M)⁺ 156 82 XII.10

¹H NMR (400 MHz, DMSO-d6) δ 11.2 (s, 1H), 7.74 (s, 1H), 7.50 (d, J = 8.4Hz, 1H), 7.4 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.19-7.03 (m, 7H), 2.05(s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.1 (M + H)⁺ 157 83XII.11

¹H NMR (400 MHz, DMSO-d6) δ 13.80-13.2 (bs, 1H), 9.50-9.0 (bs, 1H), 8.39(s, 1H), 7.92 (d, J = 5.2 Hz, 1H), 7.64 (d, J = 4.8 Hz, 1H), 7.55 (s,1H), 7.34 (s, 1H), 7.21 (s, 2H), 7.14 (d, J = 9.2 Hz, 2H), 7.05 (d, J =8.8 Hz, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.1(M + H)⁺ 158 84 VI.16

¹H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 8.13 (s, 1H), 7.53 (s, 1H),7.28 (s, 4H), 7.15- 7.14 (m, 2H), 7.08-7.04 (m, 5H), 2.04 (s, 3H), 1.82(s, 6H), 1.72 (s, 6H). LC-MS: m/z 472.1 (M + H)⁺ 159 85 XII.12

¹H NMR (400 MHz, DMSO-d6) δ 13.82 (bs, 1H), 10.41 (bs, 1H), 8.83 (bs,1H), 8.68 (s, 1H), 7.55 (s, 1H), 7.52 (d, J = 8.8 Hz, 2H), 7.33 (d, J =0.8 Hz, 1H), 7.22-7.17 (m, 2H), 7.04 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H),1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M + H)⁺ 160 86 XII.13

¹H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H), 8.37 (d, J = 2.4 Hz, 1H),8.04 (d, J = 2.0 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.47 (s, 1H), 7.32(d, J = 1.6 Hz, 1H), 7.18- 7.14 (m, 2H), 7.04 (d, J = 8.8 Hz, 2H), 2.04(s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M + H)⁺ 161 87XV.6

¹H NMR (400 MHz, DMSO-d6) δ 10.11 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H),7.41-7.39 (m, 1H), 7.35-7.31 (m, 1H), 7.23- 7.18 (m, 3H), 7.11-7.09 (m,1H), 3.93 (t, J = 8.8 Hz, 2H), 3.79 (t, J = 7.2 Hz, 2H), 3.62-3.54 (m,2H), 3.52-3.49 (m, 2H), 3.02-2.95 (m, 1H), 1.10 (d, J = 6.8 Hz, 6H). LC-MS: m/z 353.1 (M + H)⁺ 162 88 XIII.6

¹H NMR (400 MHz, DMSO-d6) δ 7.21-7.20 (m, 1H), 7.05-7.02 (m, 1H),6.89-6.85 (m, 3H), 6.82-6.74 (m, 2H), 6.65- 6.58 (m, 5H), 3.79 (bs, 1H),3.14-3.11 (m, 1H), 2.92-2.81 (m, 3H), 2.60- 2.56 (m, 1H), 2.34-2.32 (m,1H), 2.02 (s, 3H), 1.78 (s, 7H), 1.70 (s, 8H). LC-MS: m/z 480.2 (M + H)⁺163 89 XII.14

¹H NMR (400 MHz, DMSO-d6) δ 13.80 (bs, 1H), 9.12 (s, 1H), 8.23 (d, J =4.8 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.28- 7.27 (m, 3H), 7.13 (d, J =1.2 Hz, 1H), 7.06-7.03 (m, 4H), 2.04 (s, 3H), 1.82 (s, 6H), 1.71 (s,6H). LC-MS: m/z 474.3 (M + H)⁺ 168 90 XII.15

¹H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 9.12 (s, 1H), 7.70- 7.64 (m,3H), 7.36 (d, J = 7.2 Hz, 1H), 7.29 (d, J = 1.6 Hz, 1H), 7.25 (s, 1H),7.15 (dd, J₁ = 1.2 Hz, J₂ = 8.0 Hz, 1H), 7.07- 7.02 (m, 3H), 6.96 (d, J= 8.4 Hz, 1H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z474.3 (M + H)⁺ 169 91 XII.16

¹H NMR (400 MHz, DMSO-d6) δ 13.95 (bs, 1H), 13.2 (bs, 1H), 8.35 (d, J =2.4 Hz, 1H), 8.30 (dd, J₁ = 2.0 Hz, J₂ = 5.2 Hz, 1H), 8.20 (dd, J₁ = 1.6Hz, J₂ = 8.0 Hz, 1H), 8.12 (s, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.87 (dd,J₁ = 2.8 Hz, J₂ = 8.8 Hz, 1H), 7.34 (d, J = 2.4 Hz, 1H), 7.26 (dd, J₁ =2.0 Hz, J₂ = 8.8 Hz, 1H), 6.98 (d, J = 8.8 Hz, 1H), 6.80 (dd, J₁ = 4.8Hz, J₂ = 8.0 Hz, 1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS:m/z 475.2 (M + H)⁺ 170 92 VI.17

¹H NMR (400 MHz, DMSO-d6) δ 13.59 (bs, 1H), 10.58 (bs, 1H), 8.38-8.37(m, 1H), 8.36 (s, 1H), 8.27 (dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H), 7.55 (d,J = 2.4 Hz, 1H), 7.35 (dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 1H), 6.91 (dd, J₁ =4.8 Hz, J₂ = 7.6 Hz, 1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H).LC-MS: m/z 428.9 (M + H)⁺ 172 93 XIII.7

¹H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 1.2 Hz, 1H), 7.04 (d, J = 6.8Hz, 1H), 6.93-6.88 (m, 3H), 6.77 (d, J = 8.4 Hz, 1H), 6.61 (d, J = 8.4Hz, 2H), 5.70 (bs, 1H), 4.09 (bs, 1H), 3.30-3.27 (m, 3H), 3.21-3.17 (m,1H), 2.87-2.84 (m, 1H), 2.67 (m, 1H), 2.02 (s, 3H), 1.78 (s, 6H), 1.70(s, 6H). LC-MS: m/z 466.3 (M + H)⁺ 173 94 VI.18

¹H NMR (400 MHz, DMSO-d6) δ 12.6 (bs, 1H), 7.42 (s, 1H), 7.32 (s, 1H),7.16 (s, 2H), 7.09 (d, J = 7.6 Hz, 2H), 7.08- 7.00 (m, 1H), 6.93 (d, J =8.4 Hz, 2H), 4.1 (m, 1H), 2.90 (m, 1H), 2.80 (m, 1H), 2.05 (s, 3H), 1.83(s, 6H), 1.72 (s, 6H), 1.33 (s, 9H). LC-MS: m/z 523.2 (M − H)⁺ 174 95VI.18 & Com- pound 82

¹H NMR (400 MHz, DMSO-d6) δ 7.49 (s, 1H), 7.33 (s, 1H), 7.19 (s, 1H),7.11 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 3.65 (m, 1H), 3.12-3.10 (m, 1H), 2.90-2.80 (m, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s,6H). LC-MS: m/z 425.3 (M + H)⁺ 177 96 VI.20

¹H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 10.41 (bs, 1H), 8.37 (dd, J₁= 1.9 Hz, J₂ = 4.9 Hz, 1H), 8.24 (dd, J₁ = 2.0 Hz, J₂ = 7.8 Hz, 1H),7.66 (d, J = 7.8 Hz, 1H), 7.50 (s, 1H), 7.25 (t, J = 7.8 Hz, 1H), 7.03(d, J = 7.8 Hz, 1H), 6.85-6.82 (m, 1H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74(s, 6H). LC-MS: m/z 349.2 (M + H)⁺ 178 97 IV.1

¹H NMR (400 MHz, DMSO-d6) δ 12.5 (bs, 1H), 8.24 (s, 1H), 8.07 (d, J =6.8 Hz, 1H), 8.01 (s, 0.3 H), 7.84 (m, 0.6H), 7.78-7.73 (m, 2H),7.51-7.46 (m, 2H), 7.25- 7.19 (m, 1.5H), 2.09 (s, 3H), 1.98 (s, 6H),1.77 (s, 6H), 1.49 (s, 2H). LC- MS: m/z 373.1 (M + H)⁺ 182 294 98 XV.20

¹H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 9.5 (s, 1H), 8.45 (s, 1H),7.88 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.35(t, J = 1.6 Hz, 1H), 7.23 (s, 1H), 7.20-7.14 (m, 4H), 7.07 (d, J = 8.4Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 6.73-6.69 (m, 1H), 2.06 (s, 9H), 1.65(s, 6H). LC- MS: m/z 482.1 (M + H)⁺ 183 99

LC-MS: m/z 453.3 (M + H)⁺ 184 100 Int-XX

¹H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 7.75 (dd, J₁ = 0.8 Hz, J₂ =7.2 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.31 (t, J = 7.6 Hz, 2H), 7.12(d, J = 8.8 Hz, 2H), 6.90 (d, J = 9.2 Hz, 2H), 6.67 (d, J = 8.8 Hz, 2H),6.56 (d, J = 8.8 Hz, 2H), 3.18 (s, 3H), 3.13 (s, 3H), 2.02 (s, 3H), 1.80(s, 6H), 1.71 (s, 6H). LC-MS: m/z 467.3 (M + H)⁺ 185 101 VI.21

¹H NMR (400 MHz, DMSO-d6) δ 7.81 (s, 1H), 7.38 (d, J = 8.8 Hz, 1H),7.32-7.28 (m, 3H), 7.15-7.12 (m, 2H), 6.97 (d, J = 8.8 Hz, 1H), 4.72 (s,2H), 2.02 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC- MS: m/z 436.0 (M +H)⁺ 186 102 XV.7

¹H NMR (400 MHz, DMSO-d6) δ 11.59-11.3 (bs, 1H), 7.46 (d, J = 8.8 Hz,2H), 7.39 (s, 1H), 7.30 (d, J = 2.4 Hz, 1H), 7.16 (dd, J₁ = 2.0 Hz, J₂ =8.4 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 7.00 (d, J = 8.8 Hz, 2H), 4.47(d, J = 8.0 Hz, 1H), 4.33 (d, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.82 (s,6H), 1.72 (s, 6H), 1.38 (s, 3H), 1.35 (s, 3H), 1.25-1.22 (m, 1H). LC-MS:m/z 525.1 (M + H)+ 187 103 VI.22

¹H NMR (400 MHz, DMSO-d6) δ 7.66 (s, 1H), 7.36 (s, 1H), 7.26- 7.23 (m,4H), 6.96 (d, J = 8.4 Hz, 2H), 4.03 (d, J = 13.2 Hz, 1H), 3.83 (d, J =12.8 Hz, 1H), 3.21- 3.18 (m, 2H), 2.78-2.71 (m, 1H), 2.33-2.32 (m, 1H),2.15-2.02 (m, 4H), 1.95-1.79 (m, 4H), 1.74- 1.63 (m, 8H). LC-MS: m/z465.3 (M + H)⁺ 191 104 XII.17

¹H NMR (400 MHz, DMSO-d6) δ 13.40 (bs, 1H), 10.20 (s, 1H), 8.34 (dd, J₁= 1.9 Hz, J₂ = 4.9 Hz, 1H), 8.22 (dd, J₁ = 1.9 Hz, J₂ = 7.8 Hz, 1H),7.95 9bs, 1H0, 7.55 (d, J = 8.8 Hz, 2H), 7.13 (t, J = 7.8 Hz, 1H),7.05-7.00 (m, 3H), 6.85 (d, J = 7.8 Hz, 1H), 6.83-6.77 (m, 2H), 2.05 (s,3H), 1.76 (s, 6H), 1.69 (s, 6H). LC-MS: m/z 440.1 (M + H)⁺ 192 105 VI.23

¹H NMR (400 MHz, DMSO-d6) δ 7.72 (s, 1H), 7.61 (s, 1H), 7.34 (s, 1H),7.20 (s, 2H), 7.16- 7.13 (m, 3H), 6.95 (d, J = 8.4 Hz, 2H), 6.89 (s,1H), 5.07 (s, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z350.2 (M + H)⁺ 194 106 X.4

¹H NMR (400 MHz, DMSO-d6) δ 13.0 (s, 1H), 8.26-8.25 (m, 1H), 7.92 (d, J= 7.2 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.34-7.31 (m, 2H), 6.84 (dd, J₁= 4.4 Hz, J₂ = 7.2 Hz, 1H), 3.57 (s, 2H), 3.33 (m, 8H), 2.05 (s, 2H),1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 466.1 (M + H)⁺ 195 107 X.5

¹H NMR (400 MHz, DMSO-d6) δ 8.56 (dd, J₁ = 1.6 Hz, J₂ = 4.8 Hz, 1H),8.18 (d, J = 7.6 Hz, 1H), 7.46 (dd, J₁ = 4.8 Hz, J₂ = 7.6 Hz, 1H), 7.42-7.40 (m, 1H), 7.38-7.30 (m, 2H), 4.18 (s, 2H), 3.56 (s, 2H), 2.8 (s,4H), 2.55-2.54 (m, 4H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS:m/z 480.1 (M + H)⁺ 197 108 VI.24

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1.5H), 8.10 (s, 0.4H), 8.03 (s,1H), 7.52 (d, J = 7.6 Hz, 1H), 7.45-7.40 (m, 2H), 7.31 (m, 2H), 7.17 (s,1H), 7.14 (s, 2.5 H), 7.04-6.98 (m, 2H), 5.05 (s, 1H), 4.99 (s, 2H),2.04 (s, 5H), 1.90 (s, 9H), 1.72 (s, 9H). LC-MS: m/z 436.2 (M + H)⁺ 198109 XX.1

¹H NMR (400 MHz, DMSO-d6) δ 12.35 (s, 1H), 8.28 (d, J = 3.2 Hz, 1H),7.70 (d, J = 5.6 Hz, 1H), 7.47 (d, J = 1.6 Hz, 1H), 7.38 (d, J = 8.4 Hz,1H), 7.24 (d, J = 8.4 Hz, 1H), 6.84-6.81 (m, 3H), 6.43 (d, J = 8.8 Hz,2H), 3.3 (s, 3H), 3.13 (s, 3H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74 (s,6H). LC-MS: m/z 502.2 (M + H)⁺ 199 110 VI.25

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 8.15 (s, 1H), 7.52 (d, J =9.2 Hz, 1H), 7.37- 7.31 (m, 2H), 7.19-7.08 (m, 4H), 5.21 (s, 2H), 2.05(s, 3H), 1.83 (s, 6H), 1.72 (s, 1H). LC-MS: m/z 436.3 (M + H)⁺ 200 111VI.26

¹H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 10.40 (s, 1H), 8.36 (dd, J₁= 2.0 Hz, J₂ = 4.9 Hz, 1H), 8.23 (dd, J₁ = 1.9 Hz, J₂ = 7.3 Hz, 1H),8.11 (s, 1H), 7.66 (s, 1H), 7.19-7.11 (m, 3H), 7.02 (d, J = 8.3 Hz, 1H),6.95 (d, J = 7.8 Hz, 1H), 6.86- 6.83 (m, 2H), 6.70 (d, J = 7.8 Hz, 1H),1.98 (s, 3H), 1.85 (s, 6H), 1.68 (s, 6H). LC-MS: m/z 440.3 (M + H)⁺ 202112 XII.18

¹H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.2 (bs, 1H), 8.33 (d, J =2.8 Hz, 1H), 8.22 (s, 1H), 8.16 (dd, J₁ = 1.2 Hz, J₂ = 7.2 Hz, 1H), 7.67(s, 1H), 7.39 (d, J = 2.0 Hz, 1H), 7.31=7.29 (m, 1H), 6.94 (d, J = 8.4Hz, 1H), 6.74 (dd, J₁ = 5.2 Hz, J₂ = 7.6 Hz, 1H), 5.36 (bs, 2H), 2.04(s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 463.2 (M + H)⁺ 203 113XII.19

¹H NMR (400 MHz, DMSO-d6) δ 13.54 (s, 1H), 10.40 (s, 1H), 8.32 (dd, J₁ =1.9 Hz, J₂ = 4.8 Hz, 1H), 8.23 (dd, J₁ = 2.0 Hz, J₂ = 7.8 Hz, 1H), 7.61(d, J = 8.3 Hz, 1H), 7.39 (s, 1H), 7.30 (d, J = 8.3 Hz, 1H), 7.23-7.10(m, 4H), 6.84 (m, 1H), 6.75 (d, J = 8.0 Hz, 1H), 4.02 (s, 2H), 3.16 (m,1H), 1.10 (d, J = 6.8 Hz, 6H). LC-MS: m/z 347.2 (M + H)⁺ 204 114 XII.20

¹H NMR (400 MHz, DMSO-d6) δ 8.13 (d, J = 7.6 Hz, 2H), 7.48 (s, 1H), 7.42(s, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 7.26- 7.21(m, 3H), 7.09 (t, J = 7.6 Hz, 1H), 6.67 (s, 1H), 6.55 (d, J = 7.6 Hz,1H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 474.2 (M + H)⁺205 115 XII.21

¹H NMR (400 MHz, DMSO-d6) δ 13.3 (bs, 1H), 9.63 (s, 1H), 8.41 (s, 1H),8.33 (s, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.36 (s, 1H), 7.30 (d, J = 2.4Hz, 1H), 7.18-7.16 (m, 1H), 7.11 (d, J = 8.4 Hz, 1H), 7.05 (d, J = 9.2Hz, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M +H)⁺ 206 116 XII.22

¹H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 8.40 (t, J = 1.9 Hz, 2H),8.33 (s, 1H), 7.71 (m, 1H), 7.39 (s, 1H), 7.31 (s, 1H), 7.17-7.06 (m,6H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.2 (M + H)⁺207 117 XII.23

¹H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 7.99 (d, J = 6.8 Hz, 1H), 7.77(s, 1H), 7.37 (s, 1H), 7.32 (s, 1H), 7.29- 7.23 (m, 2H), 7.15 (d, J =8.8 Hz, 2H), 7.06 (d, J = 8.8 Hz, 2H), 6.9 (dd, J₁ = 2.5 Hz, J₂ = 6.9Hz, 1H), 2.05 (bs, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 474.2(M + H)⁺ 210 118 VI.27

¹H NMR (400 MHz, DMSO-d6) δ 12.88 (bs, 1H), 7.88 (s, 1H), 7.75 (s, 1H),7.57 (d, J = 8.8 Hz, 1H), 7.37 (d, J = 1.6 Hz, 1H), 7.31 (d, J = 8.0 Hz,1H), 7.21 (dd, J₁ = 2.0 Hz, J₂ = 8.8 Hz, 1H), 7.02 (s, 1H), 6.91 (dd, J₁= 1.6 Hz, J₂ = 8.8 Hz, 1H), 5.05 (s, 2H), 2.05 (s, 3H), 1.85 (s, 6H),1.73 (s, 6H). LC-MS m/z 436.2 (M + H)⁺ 211 119 XII.24

¹H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 9.5 (bs, 1H), 8.2 (bs, 1H),7.9 9bs, 1H), 7.7 (bs, 1H), 7.46 (bs, 1H), 7.40 (bs, 2H), 7.30 (bs, 1H),7.20 (bs, 1H), 7.00 (bs, 1H), 6.82 (bs, 1H), 2.05 (s, 3H), 1.90 (s, 6H),1.73 (s, 6H). LC-MS: m/z 542.2 (M + H)⁺ 212 120 XV.8

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 10.16 (bs, 1H), 8.15 (s, 1H),7.53 (s, 1H), 7.42 (d, J = 6.0 Hz, 2H), 7.32 (s, 2H), 6.92 (s, 1H), 4.71(d, J = 6.0 Hz, 1H), 4.67 (d, J = 6.0 Hz, 1H), 2.06 (s, 3H), 1.86 (s,6H), 1.73 (s, 6H), 1.4 (s, 6H). LC-MS: m/z 593.2 (M + H)⁺ 213 121 VI.28

¹H NMR (400 MHz, DMSO-d6) δ 12.25 (bs, 1H), 8.29 (s, 1H), 7.79 (s, 1H),7.63 (s, 1H), 7.40 (s, 1H), 7.22 (s, 2H), 7.19- 7.15 (m, 2H), 6.97-6.92(m, 2H), 5.23 (s, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS:m/z 350.2 (M + H)⁺ 214 122 VI.29

¹H NMR (400 MHz, DMSO-d6) δ 13.45 (bs, 1H), 8.59 (d, J = 3.6 Hz, 1H),8.09 (d, J = 6.8 Hz, 1H), 7.36-7.30 (m, 3H), 7.16-7.11 (m, 2H), 7.07 (d,J = 8.4 Hz, 2H), 6.90 (d, J = 7.6 Hz, 2H), 4.39 (s, 2H), 2.03 (s, 3H),1.81 (s, 6H), 1.71 (s, 6H). LC- MS: m/z 473.2 (M + H)⁺ 215 123 XV.9

¹H NMR (400 MHz, DMSO-d6) δ 12.39 (s, 1H), 7.94 (s, 1H), 7.39 (d, J =2.0 Hz, 1H), 7.33- 7.24 (m, 4H), 6.92 (d, J = 8.8 Hz, 2H), 4.20-3.99 (m,1H), 3.98-3.62 (m, 1H), 3.10-2.92 (m, 2H), 2.45-2.37 (m, 1H), 2.06 (s,3H), 2.01-1.97 (m, 1H), 1.85 (s, 6H), 1.73 (s, 6H), 1.69-1.55 (m, 2H),1.44-1.39 (m, 1H). LC- MS: m/z 493.2 (M + H)⁺ 217 124 VI.30

¹H NMR (400 MHz, DMSO-d6) δ 12.15 (bs, 1H), 7.52 (s, 1H), 7.32 (s, 1H),7.18 (s, 3H), 7.02 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 6.84-6.82 (m, 1H), 6.12-6.10 (m, 1H), 5.44 (s, 2H), 2.04 (s, 3H), 1.82 (s,6H), 1.72 (s, 6H). LC-MS: m/z 461.2 (M + H)⁺ 218 125 VI.31

¹H NMR (400 MHz, DMSO-d6) δ 12.41 (s, 1H), 8.33 (dd, J₁ = 2.0 Hz, J₂ =4.8 Hz, 1H), 7.75 (dd, J₁ = 2.0 Hz, J₂ = 7.2 Hz, 1H), 7.42 (s, 1H), 7.31(s, 1H), 7.17 (s, 2H), 6.94 (d, J = 8.8 Hz, 2H), 6.89- 6.86 (m, 3H),3.32 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.1(M + H)⁺ 219 126 VI.32

¹H NMR (400 MHz, DMSO-d6) δ 12.89 (s, 1H), 7.43 (d, J = 8.4 Hz, 1H),7.28 (s, 2H), 7.20 (d, J = 3.2 Hz, 1H), 7.09 (S, 3H), 6.86 (dd, J₁ = 1.6Hz, J₂ = 8.4 Hz, 1H), 6.36 (d, J = 2.8 Hz, 1H), 4.9 (s, 2H), 2.04 (s,3H), 1.81 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 435.2 (M + H)⁺ 220 127 VI.33

¹H NMR (400 MHz, DMSO-d6) δ 12.00 (bs, 1H), 7.82 (d, J = 6.4 Hz, 2H),7.67 (s, 1H), 7.34 (s, 1H), 7.21-7.17 (m, 3H), 6.89 (d, J = 5.6 Hz, 2H),6.74 (d, J = 7.6 Hz, 1H), 5.16 (s, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73(s, 6H). LC-MS: m/z 462.3 (M + H)⁺ 221 128 VI.34

¹H NMR (400 MHz, DMSO-d6) δ 12.75 (bs, 1H), 8.03 (s, 1H), 7.62 (d, J =2.8 Hz, 2H), 7.33 (d, J = 1.2 Hz, 1H), 7.19- 7.15 (m, 3H), 6.88-6.86 (m,1H), 6.78 (s, 1H), 6.61-6.56 (m, 1H), 5.46 (s, 2H), 2.05 (s, 3H), 1.84(s, 6H), 1.73 (s, 6H). LC- MS: m/z 462.2 (M + H)⁺ 226 129 XII.25

¹H NMR (400 MHz, DMSO-d6) δ 12.5 (bs, 1H), 8.38 (s, 1H), 8.18 (d, J =7.6 Hz, 1H), 8.11 (d, J = 3.6 Hz, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.34(dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 6.74 (dd,J₁ = 4.8 Hz, J₂ = 7.2 Hz, 1H), 5.38 (s, 2H), 2.04 (s, 3H), 1.84 (d, J =2.4 Hz, 6H), 1.69 (s, 6H). LC-MS: m/z 464.2 (M + H)⁺ 227 130 VI.35

¹H NMR (400 MHz, DMSO-d6) δ 12.9 (s, 1H), 7.32-7.26 (m, 3H), 7.09- 7.07(m, 2H), 6.95 (dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz, 1H), 6.93 (d, J = 7.2 Hz,1H), 6.35 (d, J = 2.4 Hz, 1H), 4.97 (s, 2H), 2.03 (s, 3H), 1.80 (s, 6H),1.71 (s, 6H). LC-MS: m/z 435.2 (M + H)⁺ 228 131 XII.26

¹H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.2 (s, 1H), 8.40- 8.30 (m,2H), 7.40-7.39 (m, 2H), 7.38-7.30 (m, 1H), 699-6.90 (m, 2H), 6.90-6.80(m, 1H), 6.80- 6.70 (m, 1H), 4.30 (s, 2H), 3.36 (m, 2H), 2.9 (m, 2H),2.05 (s, 3H), 1.85 (d, J = 2.4 Hz, 6H), 1.73 (s, 6H). LC- MS: m/z 514.2(M + H) 233 132 XX.2

¹H NMR (400 MHz, DMSO-d6) δ 12.53 (bs, 1H), 8.35 (dd, J₁ = 1.9 Hz, J₂ =4.4 Hz, 1H), 7.83 (dd, J₁ = 2.0 Hz, J₂ = 7.8 Hz, 1H), 7.43 (d, J = 2.4Hz, 1H), 7.34 (dd, J₁ = 1.9 Hz, J₂ = 8.8 Hz, 1H), 7.23 (d, J = 8.4 Hz,1H), 7.0-6.92 (m, 2H), 6.3 (dd, J₁ = 1.9 Hz, J₂ = 8.3 Hz, 1H), 6.1 (dd,J₁ = 1.9 Hz, J₂ = 8.3 Hz, 1H), 6.04 (d, J = 2.5 Hz, 1H), 3.34 (s, 3H),3.07 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 502.3(M + H)⁺ 236 133 XX.3

¹H NMR (400 MHz, DMSO-d6) δ 12.60 (bs, 1H), 8.30 (dd, J₁ = 2.0 Hz, J₂ =4.9 Hz, 1H), 7.82 (dd, J₁ = 1.5 Hz, J₂ = 7.4 Hz, 1H), 7.71 (s, 1H), 7.38(d, J = 2.9 Hz, 2H), 7.32 (dd, J₁ = 1.9 Hz, J₂ = 8.3 Hz, 1H), 6.88 (m,2H), 5.27 (s, 2H), 3.25 (s, 2H), 2.08 (s, 3H), 1.83 (s, 6H), 1.72 (s,6H). LC-MS: m/z 477.2 (M + H)⁺ 240 134 XII.27

¹H NMR (400 MHz, DMSO-d6) δ 13.82-13.2 (bs, 1H), 10.44 (s, 1H), 8.37(dd, J₁ = 1.6 Hz, J₂ = 4.4 Hz, 1H), 8.19 (dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz,1H), 7.60 (d, J = 1.6 Hz, 1H), 7.42 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 2H),7.34 (dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz, 1H), 7.11 (d, J = 8.4 Hz, 1H), 6.78(dd, J₁ = 4.8 Hz, J₂ = 8.0 Hz, 1H), 5.26 (s, 2H), 2.04 (s, 3H), 1.82 (d,J = 6.8 Hz, 6H), 1.71 (s, 6H). LC-MS: m/z 463.2 (M + H)⁺ 241 135 VI.38

¹H NMR (400 MHz, DMSO-d6) δ 12.61 (s, 1H), 8.39 (dd, J₁ = 2.0 Hz, J₂ =4.8 Hz, 1H), 7.89 (dd, J₁ = 2.0 Hz, J₂ = 7.6 Hz, 1H), 7.46 (s, 1H), 7.29(dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz, 2H), 7.16 (dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz,1H), 7.07- 6.98 (m, 2H), 6.61 (t, J = 8.4 Hz, 2H), 6.41 (t, J = 1.6 Hz,1H), 3.36 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z488.1 (M + H)⁺ 243 136 VI.39

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 8.23 (s, 1H), 8.13 (d, J =6.9 Hz, 1H), 7.52 (s, 1H), 7.33 (s, 1H), 7.19 (m, 3H), 7.04 (d, J = 8.8Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s,6H). LC-MS: m/z 475.1 244 137 XIII.10

¹H NMR (400 MHz, DMSO-d6) δ 8.59 (dd, J₁ = 1.6 Hz, J₂ = 4.4 Hz, 1H),8.22 (dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H), 7.49 (dd, J₁ = 4.8 Hz, J₂ = 8.0Hz, 1H), 7.20 (d, J = 2.0 Hz, 1H), 7.12 (dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz,1H), 6.69 (d, J = 8.8 Hz, 1H), 5.26 (d, J = 7.2 Hz, 1H), 4.45 (s, 2H),4.24-4.20 (m, 1H), 3.36-3.20 (m 2H), 3.10- 3.02 (m, 2H), 2.36-2.32 (m,1H), 2.02 (s, 3H), 1.78 (s, 6H), 1.67 (s, 6H). LC-MS: m/z 466.20 (M +H)⁺ 245 138 VI.40

¹H NMR (400 MHz, DMSO-d6) δ 12.8-12.0 (bs, 1H), 8.2 (s, 1H), 7.87 (s,1H), 7.67 (d, J = 5.6 Hz, 1H), 7.17 (d, J = 8.8 Hz, 2H), 6.95-6.89 (m,4H), 6.85-6.82 (m, 3H), 3.3 (s, 3H), 2.03 (s, 3H), 1.82 (s, 6H), 1.71(s, 6H). LC-MS: m/z 454.1 (M + H)⁺ 246 139 XX.4

¹H NMR (400 MHz, DMSO-d6) δ 12.49 (s, 1H), 8.34 (s, 1H), 7.77- 7.76 (m,1H), 7.24-7.22 (m, 2H), 6.93-6.87 (m, 7H), 3.19 (s, 3H), 2.04 (s, 3H),1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 468.1 (M + H)⁺ 247 140 XX.5

¹H NMR (400 MHz, DMSO-d6) δ 12.57 (s, 1H), 8.36 (dd, J₁ = 2.0 Hz, J₂ =4.9 Hz, 1H), 7.86 (dd, J₁ = 1.4 Hz, J₂ = 7.3 Hz, 1H), 7.23 (d, J = 8.3Hz, 2H), 7.09 (d, J = 8.4 Hz, 1H), 6.95 (m, 3H), 6.5 (m, 2H), 6.39 (t, J= 2.4 Hz, 1H), 3.35 (s, 3H), 3.16 (s, 3H), 2.04 (bs, 3H), 1.82 (s, 6H),1.69 (s, 6H). LC-MS: m/z 468.1 (M + H)⁺ 248 141 XIII.11

¹H NMR (400 MHz, DMSO-d6) δ 10.80- 12.80 (bs, 1H), 8.54 (d, J = 3.4 Hz,1H), 8.14 (d, J = 6.8 Hz, 1H), 7.42 (m, 1H), 7.16 (d, J = 2.4 Hz, 1H),7.09 (dd, J1 = 1.9 Hz, J2 = 8.3 Hz, 1H), 6.67 (d, J = 8.8 Hz, 1H), 4.87(d, J = 8.0 Hz, 1H), 4.16 (m, 2H), 3.57 (bs, 1H), 2.98 (d, J = 9.2 Hz,1H), 2.7 (m, 1H), 2.57 (m, 3H), 2.08 (s, 3H), 1.82-1.77 (m, 9H), 1.73(m, 7H), 1.58-1.49 (m, 3H). LC- MS: m/z 480.1 (M + H)⁺ 249 142 XII.28

¹H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.6 (bs, 1H), 8.22- 8.21 (m,1H), 8.16 (dd, J₁ = 1.6 Hz, J₂ = 7.2 Hz, 1H), 7.47-7.38 (m, 4H), 7.27(d, J = 8.4 Hz, 1H), 6.72 (dd, J₁ = 4.4 Hz, J₂ = 7.6 Hz, 1H), 6.52 (d, J= 8.8 Hz, 2H), 3.17 (s, 3H), 2.07 (s, 3H), 1.89 (s, 6H), 1.74 (s, 6H).LC-MS: m/z 487.2 (M + H)⁺ 250 143 VI.42

¹H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 9.80 (s, 1H), 7.88 (s, 1H),7.39 (d, J = 1.4 Hz, 1H), 7.33-7.27 (m, 4H), 6.98 (d, J = 8.3 Hz, 2H),4.20-4.17 (bs, 2H), 3.49- 3.42 (m, 1H), 2.85-2.70 (m, 3H), 2.06 (s, 3H),1.91-1.85 (m, 7H), 1.84- 1.72 (m, 8H), 1.57-1.40 (m, 1H). LC-MS: m/z479.1 (M + H)⁺² 252 144 VI.43

¹H NMR (400 MHz, DMSO-d6) δ 12.72 (s, 1H), 7.99 (s, 1H), 7.96 (d, J =1.6 Hz, 1H), 7.80 (dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H), 7.68-7.61 (m, 2H),7.42-7.35 (m, 3H), 7.29 (d, J = 2.0 Hz, 1H), 7.17 (dd, J₁ = 2.4 Hz, J₂ =8.8 Hz, 1H), 3.30 (s, 3H), 2.08 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H).LC-MS: m/z 487.1 (M − H)⁺ 254 145 XV.11

¹H NMR (400 MHz, DMSO-d6) δ 13.72 (bs, 1H), 10.74 (bs, 1H), 10.02 (s,1H), 8.46 (dd, J₁ = 1.9 Hz, J₂ = 5.0 Hz, 1H), 8.30 (dd, J₁ = 2.0 Hz, J₂= 7.8 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.88 (d, J = 8.8 Hz, 2H), 7.69(d, J = 8.8 Hz, 2H), 7.32 (d, J = 8.8 Hz, 2H), 6.96 (m, 1H), 2.06 (s,3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 468.1 (M + H)⁺ 255 146 XV.12

¹H NMR (400 MHz, DMSO-d6) δ 13.00-12.8 (bs, 1H), 9.77 (s, 1H), 7.85 (d,J = 6.4 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.66-7.64 (m, 3H), 7.50- 7.42(m, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 8.8 Hz, 2H), 6.52 (d, J= 8.8 Hz, 2H), 3.26 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H).LC-MS: m/z 481.1 (M + H)⁺ 258 147 XV.13

¹H NMR (400 MHz, DMSO-d6) δ 9.87 (s, 1H), 8.43 (bs, 1H), 7.95 (d, J =6.9 Hz, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.29(d, J = 8.3 Hz, 2H), 7.19 (m, 1H), 6.82 (d, J = 8.3 Hz, 2H), 3.38 (s,3H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 482.25 (M +H)⁺ 259 148 XV.14

¹H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.93 (s, 1H), 9.71 (s, 1H),8.03 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.79 (m, 1H), 7.70(d, J = 8.8 Hz, 2H), 7.51 (d, J = 7.3 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H),7.12 (d, J = 8.3 Hz, 1H), 2.06 (s, 3H), 1.83 (s, 6H), 1.74 (s, 6H).LC-MS: m/z 468.20 (M + H)⁺ 260 149 XX.6

¹H NMR (400 MHz, DMSO-d6) δ 12.00-11.8 (bs, 1H), 7.65 (d, J = 8.0 Hz,2H), 7.5 (d, J = 8.4 Hz, 1H), 7.4-7.35 (m, 1H), 7.32-7.2 (m, 1H),7.25-7.15 (m, 3H), 6.86 (d, J = 8.4 Hz, 2H), 6.42 (bs, 2H), 3.16 (s,3H), 3.07 (s, 3H), 2.02 (s, 3H), 1.78 (s, 6H), 1.72 (s, 6H). LC-MS: m/z495.2 (M + H)⁺ 261 150 XII.29

¹H NMR (400 MHz, DMSO-d6) δ 10.4 (bs, 1H), 7.62 (t, J = 8.0 Hz, 1H),7.54 (s, 1H), 7.34-7.31 (m, 3H), 7.24 (dd, J₁ = 1.2 Hz, J₂ = 8.4 Hz,1H), 7.17- 7.09 (m, 2H), 7.04 (s, 1H), 6.97 (d, J = 7.2 Hz, 1H), 6.63(d, J = 8.4 Hz, 1H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS:m/z 474.1 (M + H)⁺ 263 151 XII.31

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 11.67 (s, 1H), 9.07 (s, 1H),8.52 (d, J = 2.0 Hz, 1H), 8.28 (d, J = 2.4 Hz, 1H), 7.60 (s, 1H),7.51-7.45 (m, 3H), 7.34 (s, 1H), 7.22 (s, 1H), 1.91 (s, 2H), 1.72-1.64(m, 13H). LC-MS: m/z 506.0 (M + H)⁺ 266 152 XX.7

¹H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 8.43 (dd, J₁ = 2.0 Hz, J₂ =4.4 Hz, 1H), 7.96 (dd, J₁ = 2.0 Hz, J₂ = 7.6 Hz, 1H), 7.30 (d, J = 8.8Hz, 2H), 7.08-7.04 (m, 3H), 6.59-6.58 (m, 2H), 6.37 (s, 1H), 3.37 (s,3H), 3.2 (s, 3H), 2.06 (s, 3H), 1.83 (d, J = 2.4 Hz, 6H), 1.73 (s, 6H).LC-MS: m/z 536.1 (M + H)⁺ 267 153 XII.32

¹H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 8.83 (s, 1H), 8.54 (dd, J₁ =0.8 Hz, J₂ = 12.0 Hz, 2H), 8.14 (s, 1H), 7.91 (s, 1H), 7.41 (d, J = 2.0Hz, 1H), 7.35-7.28 (m, 2H), 6.84 (s, 1H), 6.73 (d, J = 13.6 Hz, 2H),2.05 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 542.2 (M + H)⁺ 268154 XII.24

¹H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 11.58 (s, 1H), 9.5 (s, 1H),7.6 (t, J = 7.2 Hz, 2H), 7.49-7.43 (m, 5H), 6.63 (d, J = 8.4 Hz, 1H),1.99 (s, 3H), 1.72-1.60 (m, 12H). LC-MS: m/z 506.2 (M + H)⁺ 270 155 XX.8

¹H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 7.80 (m, 1H), 7.60 (m, 1H),7.29 (m, 4H), 6.83 (t, J = 9.3 Hz, 4H), 6.57 (d, J = 8.8 Hz, 2H), 3.19(s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H). LC-MS: m/z (M + H)⁺LC-MS: m/z 454.1 (M + H)⁺ 271 156 XX.9

¹H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 8.52 (dd, J₁ = 1.6 Hz, J₂ =4.4 Hz, 1H), 8.03 (dd, J₁ = 1.6 Hz, J₂ = 7.2 Hz, 1H), 7.21-7.16 (m, 4H),7.12 (d, J = 8.8 Hz, 2H), 6.44 (d, J = 8.8 Hz, 2H), 3.44 (s, 3H), 3.06(s, 3H), 2.02 (s, 3H), 1.79 (s, 6H), 1.67 (s, 6H). LC-MS: m/z 536.1 (M +H)⁺ 272 157 XV.15

¹H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 10.16 (s, 1H), 9.6 (bs, 1H),7.89 (m, 3H), 7.77 (d, J = 9.3 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.38(m, 1H), 7.23 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.8 Hz, 1H), 6.74 (m,1H), 2.08 (s, 3H), 1.90 (s, 6H), 1.76 (s, 6H). LC-MS: m/z 467.1 (M + H)⁺273 158 XX.10

¹H NMR (400 MHz, DMSO-d6) δ 12.9 (bs, 1H), 7.85 (dd, J₁ = 1.2 Hz, J₂ =8.8 Hz, 1H), 7.70- 7.66 (m, 1H), 7.46-7.39 (m, 2H), 7.10-7.04 (m, 3H),6.78-6.73 (m, 2H), 6.39 (d, J = 8.8 Hz, 2H), 3.31 (s, 3H), 3.02 (s, 3H),2.02 (s, 3H), 1.74 (s, 6H), 1.67 (s, 6H). LC-MS: m/z 535.1 (M + H)⁺ 274159 XV.16

¹H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 9.71 (s, 1H), 7.94- 7.91 (m,1H), 7.46-7.42 (m, 1H), 7.34-7.25 (m, 5H), 6.85 (t, J = 7.2 Hz, 1H),1.56-1.48 (m, 5H), 1.33-1.12 (m, 6H), 0.92- 0.74 (m, 7H). LC-MS: m/z369.1 (M + H)⁺ 275 160 XX.11

¹H NMR (400 MHz, DMSO-d6) δ 12.72 (s, 1H), 7.68-7.65 (m, 2H), 7.53 (t, J= 8.4 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.26-7.19 (m, 2H), 7.09 (d, J =8.8 Hz, 2H), 6.88 (dd, J₁ = 3.2 Hz, J₂ = 8.8 Hz, 1H), 6.55 (d, J = 9.6Hz, 1H), 3.29 (s, 3H), 3.18 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73(s, 6H). LC-MS: m/z 468.1 (M + H)⁺ 276 161 XX.12

¹H NMR (400 MHz, DMSO-d6) δ 12.79 (s, 1H), 7.79 (dd, J₁ = 1.5 Hz, J₂ =7.3 Hz, 1H), 7.62 (t, J = 1.5 Hz, 1H), 7.35 (m, 2H), 7.14 (d, J = 8.8Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 6.63 (d, J = 8.8 Hz, 2H), 6.57 (d, J= 9.3 Hz, 2H), 3.26 (m, 1H), 3.20 (s, 3H), 3.18 (s, 3H), 1.48 (m, 4H),1.23 (m, 4H), 0.83 (m, 6H). LC-MS: m/z 488.7 (M + H)⁺ 277 162 XX.13

¹H NMR (400 MHz, DMSO-d6) δ 12.79 (s, 1H), 7.78 (d, J = 7.6 Hz, 1H),7.60-7.59 (m, 1H), 7.37-7.25 (m, 4H), 7.17- 7.14 (m, 1H), 7.08-7.00 (m,5H), 6.72 (d, J = 8.8 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 3.2 (s, 6H),3.08-3.04 (m, 1H), 1.1 (d, J = 6.8 Hz, 6H). LC-MS: m/z 451.1 (M + H)⁺278 163

LC-MS: m/z 495.2 (M + H)⁺ 279 164

LC-MS: m/z 523.6 (M + H)⁺ 282 165

LC-MS: m/z 453.1 (M + H)⁺ 284 166 XII.36

¹H NMR (400 MHz, DMSO-d6) δ 11.90 (bs, 1H), 7.88 (d, J = 7.4 Hz, 1H),7.46 (s, 1H), 7.30 (d, J = 2.4 Hz, 1H), 7.11 (m, 4H), 6.91 (m, 4H), 6.63(m, 1H), 2.05 (s, 3H), 1.85 (s, 6H), 1.72 (s, 6H). LC-MS: 474.0 (M + H)⁺285 167 XV.17

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.90 (bs, 1H), 7.93 (d, J =8.0 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.45- 7.43 (m, 2H), 7.36 (d, J =7.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 6.86 (t, J = 7.2 Hz, 1H), 2.07(s, 9H), 1.66 (s, 6H). LC- MS: m/z 391.0 (M + H)⁺ 286 168 XX.14

¹H NMR (400 MHz, DMSO-d6) δ 12.7 (bs, 1H), 7.75 (dd, J₁ = 1.6 Hz, J₂ =8.0 Hz, 1H), 7.61- 7.57 (m, 1H), 7.43 (d, J = 2.0 Hz, 1H), 7.43-7.23 (m,3H), 6.81 (t, J = 9.2 Hz, 3H), 6.57 (d, J = 8.8 Hz, 2H), 3.19 (s, 3H),2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.0 (M + H)⁺ 287169 VI.46

¹H NMR (400 MHz, DMSO-d6) δ 13.60- 12.00 (bs, 1H), 9.50 (s, 1H), 8.34(s, 1H), 7.87 (dd, J₁ = 1.2 Hz, J₂ = 8.0 Hz, 1H), 7.36-7.03 (m, 10H),6.70 (t, J = 7.2 Hz, 1H), 4.06-4.02 (m, 2H), 2.88-2.83 (m, 3H), 1.68-1.55 (m, 4H), 1.33-1.10 (m, 5H), 0.89 (t, J = 7.2 Hz, 6H). LC-MS: m/z444.1 (M + H)⁺ 288 170 XV.18

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 11.9 (bs, 1H), 10.38 (bs,1H), 9.8 (s, 1H), 7.96 (m, 4H), 7.7 (bs, 1H), 7.47 (m, 2H), 7.36 (m,2H), 6.92 (m, 1H), 6.6 (bs, 1H), 3.44 (m, 4H), 1.53 (m, 4H), 1.27 (m,4H), 0.84 (m, 6H). LC-MS: m/z 460.1 (M + H)⁺ 289 71 XII.37

¹H NMR (400 MHz, DMSO-d6) δ 12.85 (bs, 1H), 7.77 (dd, J₁ = 1.2 Hz, J₂ =8.0 Hz, 1H), 7.61- 7.57 (m, 1H), 7.35-7.32 (m, 1H), 7.28 (d, J = 8.0 Hz,1H), 7.13 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 9.6 Hz, 2H), 6.67 (d, J =8.8 Hz, 2H), 6.55 (d, J = 6.8 Hz, 2H), 3.66-3.61 (m, 2H), 3.13 (s, 3H),2.03 (s, 3H), 1.79 (s, 6H), 1.71 (s, 6H), 1.13 (t, J = 7.6 Hz, 3H).LC-MS: m/z 481.1 (M + H)⁺ 290 172 XII.38

¹H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 9.48 (s, 1H), 7.87 (dd, J₁ =1.2 Hz, J₂ = 7.6 Hz, 1H), 7.35 (t, J = 6.8 Hz, 1H), 7.26 (d, J = 8.8 Hz,2H), 7.15 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.8 Hz, 1H), 6.99-6.94 (m,4H), 6.70 (t, J = 7.2 Hz, 1H), 3.23 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H),1.78 (s, 6H). LC-MS: m/z 453.1 (M + H)⁺ 291 173 VI.47

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 8.48 (s, 1H), 7.83 (d, J = 7.2Hz, 1H), 7.70- 7.65 (m, 3H), 7.31-7.25 (m, 3H), 7.16-7.13 (m, 4H), 3.84(s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 478.1 (M +H)⁺ 292 174 VI.48

¹H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 9.40 (s, 1H), 8.09 (s, 1H),7.87 (d, J = 1.4 Hz, 1H), 7.33 (t, J = 6.8 Hz, 1H), 7.15-7.08 (m, 8H),7.01-6.98 (m, 3H), 6.70- 6.65 (m, 4H), 3.58 (t, J = 7.8 Hz, 2H),1.58-1.51 (m, 2H), 1.38-1.28 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H), LC-MS:m/z 452.1 (M + H)⁺ 293 175 XV.19

¹H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 9.50 (bs, 1H), 8.36 (s, 1H),7.88 (dd, J₁ = 1.4 Hz, J₂ = 7.8 Hz, 1H), 7.36 (t, 1H), 7.21-7.13 (m,6H), 7.06-7.01 (m, 3H), 6.70 (t, J = 7.8 Hz, 1H), 3.30 (m, 4H),1.52-1.49 (m, 4H), 1.23 (m, 4H), 0.86-0.84 (m, 6H). LC- MS: m/z 460.1(M + H)⁺ 294 176 XV.20

¹H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 9.5 (s, 1H), 8.45 (s, 1H),7.88 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.35(t, J = 1.6 Hz, 1H), 7.23 (s, 1H), 7.20-7.14 (m, 4H), 7.07 (d, J = 8.4Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 6.73-6.69 (m, 1H), 2.06 (s, 9H), 1.65(s, 6H). LC- MS: m/z 482.1 (M + H)⁺ 295 177 VI.49

¹H NMR (400 MHz, DMSO-d6) δ 12.83 (bs, 1H), 9.42 (s, 1H), 7.99 (s, 1H),7.85 (dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H), 7.32 (t, J = 8.8 Hz, 1H), 7.20(d, J = 8.8 Hz, 2H), 7.11-7.04 (m, 4H), 7.01-6.96 (m, 3H), 6.67 (t, J =7.6 Hz, 1H), 2.13-2.12 (m, 1H), 1.66 (s, 2H), 1.50-1.32 (m, 8H), 1.17(s, 2H), 0.85 (s, 6H). LC-MS: m/z 467.1 (M + H)⁺ 296 178 XX.15

¹H NMR (400 MHz, DMSO-d6) δ 12.79 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H),7.58 (t, J = 6.8 Hz, 1H), 7.33-7.29 (m, 2H), 7.11 (d, J = 8.8 Hz, 2H),6.89 (d, J = 8.8 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz,2H), 3.18 (s, 3H), 3.12 (s, 3H), 2.10 (m, 1H), 1.62 (s, 2H), 1.46-1.30(m, 8H), 1.16 (s, 2H), 0.83 (s, 6H). LC-MS: m/z 495.1 (M + H)⁺ 297 179XV.21

¹H NMR (400 MHz, DMSO-d6) δ 12.84 (bs, 1H), 10.04 (s, 1H), 9.23 (s, 1H),7.89 (d, J = 8.3 Hz, 2H), 7.78 (d, J = 8.3 Hz, 2H), 7.67 (m, 3H), 7.51(d, J = 8.3 Hz, 2H), 7.40 (d, J = 6.8 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H),2.08 (s, 3H), 1.91 (s, 6H), 1.76 (s, 6H). LC-MS: m/z 468.0 (M + H)⁺ 298180 XI.17

¹H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.27 (s, 1H), 8.51 (d, J =13.6 Hz, 2H), 8.34 (s, 1H), 8.21 (d, J = 6.8 Hz, 1H), 7.58 (d, J = 7.2Hz, 2H), 7.40-7.35 (m, 4H), 7.25 (d, J = 7.2 Hz, 2H), 6.81 (bs, 1H),2.04 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 483.1 (M + H)⁺ 299181 XIX.3

¹H NMR (400 MHz, DMSO-d6) δ 13.80- 12.80 (bs, 1H), 10.05 (bs, 1H), 9.86(s, 1H), 8.25 (d, J = 2.8 Hz, 1H), 8.15 (d, J = 7.2 Hz, 1H), 7.53 (d, J= 8.4 Hz, 2H), 7.34 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.71(dd, J₁ = 4.8 Hz, J₂ = 8.0 Hz, 1H), 6.58 (d, J = 8.8 Hz, 2H), 5.85 (bs,1H), 3.82 (bs, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z497.1 (M + H)⁺ 300 182 XIX.1

¹H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.13 (s, 1H), 8.50 (s, 1H),8.43 (s, 1H), 7.68 (m, 3H), 7.37 (m, 5H), 7.25 (d, J = 8.3 Hz, 2H), 6.98(d, J = 8.3 Hz, 1H), 2.05 (s, 3H), 1.76 (s, 6H), 1.73 (s, 6H). LC-MS:m/z 483.1 (M + H)⁺ 301 183 XV.22

¹H NMR (400 MHz, DMSO-d6) δ 9.76 (bs, 1H), 8.32 (bs, 1H), 8.25 (m, 1H),7.95 (d, J = 8.8 Hz, 2H), 7.89 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.3 Hz,1H), 7.45 (s, 1H), 7.37 (m, 1H), 6.86 (m, 1H), 2.07 (s, 3H), 1.88 (s,6H), 1.74 (s, 6H). LC-MS: m/z 502.0 (M + H)⁺ 302 184 XV.23

¹H NMR (400 MHz, DMSO-d6) δ 14.00- 13.00 (bs, 1H), 10.36 (s, 1H), 10.02(s, 1H), 8.36 (m, 1H), 8.24 (d, J = 7.8 Hz, 1H), 7.65 (d, J = 8.3 Hz,2H), 7.52 (d, J = 8.8 Hz, 2H), 7.28-7.25 (m, 4H), 6.86-6.83 (m, 1H),3.56 (s, 2H), 2.03 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 482.1(M + H)⁺ 303 185 XV.24

¹H NMR (400 MHz, DMSO-d6) δ 12.93 (bs, 1H), 9.91 (s, 1H), 8.81 (s, 1H),7.88 (d, J = 8.8 Hz, 2H), 7.75 (s, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.48-7.39 (m, 3H), 7.30 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 2.05(s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 467.1 (M + H)⁺ 304 186Int-VI

¹H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 9.66 (s, 1H), 7.90 (d, J =8.4 Hz, 1H), 7.40- 7.38 (m, 3H), 7.26-7.24 (m, 5H), 7.20 (d, J = 8.4 Hz,2H), 6.82 (t, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H).LC-MS: m/z 507.1 (M + H)⁺ 305 187 XX.16

¹H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 7.75 (m, 1H), 7.59 (t, 1H),7.32-7.30 (m, 2H), 7.12-7.08 (m, 2H), 6.93 (t, J = 8.3 Hz, 4H), 6.74 (d,J = 8.3 Hz, 2H), 6.64 (d, J = 7.3 Hz, 2H), 6.58 (d, J = 7.8 Hz, 3H),3.56-3.54 (m, 2H), 3.19 (s, 3H), 3.16 (s, 3H), 1.51-1.49 (m, 2H), 1.33-1.28 (m, 2H), 0.87 (t, J = 7.3 Hz, 3H), LC-MS: m/z 480.1 (M + H)⁺ 306188 XVIII.1

¹H NMR (400 MHz, DMSO-d6) δ 13.79 (bs, 1H), 10.77 (s, 1H), 10.03 (s,1H), 8.44-8.43 (m, 1H), 8.28 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H), 7.89(d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H),7.03-6.96 (m, 3H), 1.99 (s, 3H), 1.76 (s, 6H), 1.68 (s, 6H). LC-MS: m/z504.0 (M + H)⁺ 307 189 XIX.2

¹H NMR (400 MHz, DMSO-d6) δ 12.95 (bs, 1H), 9.50 (bs, 1H), 8.60 (s, 1H),8.52 (s, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.46 (d, J = 8.3 Hz, 2H), 7.36(m, 3H), 7.26 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.8 Hz, 2H), 7.05 (d, J= 8.3 Hz, 1H), 6.70 (t, J = 7.4 Hz, 1H), 2.05 (s, 3H), 1.84 (s, 6H),1.73 (s, 6H). LC-MS: m/z 482.0 (M + H)⁺ 308 190 Int- XVIII

¹H NMR (400 MHz, DMSO-d6) δ 13.25 (bs, 1H), 10.02 (s, 1H), 9.75 (s, 1H),7.92 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.49-7.41 (m, 2H),7.28 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz,2H), 6.96 (t, J = 7.2 Hz, 1H), 2.00 (s, 3H), 1.77 (s, 6H), 1.69 (s, 6H).LC-MS: m/z 503.0 (M + H)⁺ 309 191 VI.50

¹H NMR (400 MHz, DMSO-d6) δ 12.8 (s, 1H), 7.81 (d, J = 7.2 Hz, 1H),7.66-7.62 (m, 1H), 7.41-7.32 (m, 6H), 7.27 (d, J = 8.8 Hz, 2H), 6.48 (d,J = 8.0 Hz, 2H), 3.22 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H).LC- MS: m/z 462.1 (M + H)⁺ 310 192 XX.17

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.8 (bs, 1H), 7.9 (m, 1H),7.40-7.30 (m, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.21-7.19 (m, 3H), 7.08 (d,J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 6.90- 6.80 (m, 1H), 3.34 (s,3H), 2.02 (s, 3H), 1.81 (s, 6H), 1.70 (s, 6H). LC-MS: m/z 481.0 (M + H)⁺311 193 XII.39

¹H NMR (400 MHz, DMSO-d6) δ 10.40- 10.00 (bs, 1H), 7.57 (t, J = 8.0 Hz,1H), 7.50-7.40 (m, 2H), 7.28 (d, J = 7.2 Hz, 1H), 7.20 (d, J = 8.8 Hz,2H), 7.02 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.4 Hz, 1H), 6.84 (d, J =8.8 Hz, 2H), 3.22 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).LC-MS: m/z m/z 454.0 (M + H)⁺ 312 194 XVIII.2

¹H NMR (400 MHz, DMSO-d6) δ 13.10 (bs, 1H), 9.97 (s, 1H), 9.76 (s, 1H),7.97 (d, J = 8.8 Hz, 2H), 7.77 (t, J = 7.6 Hz, 1H), 7.64 (d, J = 8.8 Hz,2H), 7.51 (d, J = 7.2 Hz, 1H), 7.19 (d, J = 8.8 Hz, 2H), 7.08 (d, J =8.0 Hz, 1H), 7.02 (d, J = 8.4 Hz, 2H), 1.99 (s, 3H), 1.76 (s, 6H), 1.68(s, 6H). LC-MS: m/z 504.2 (M + H)⁺ 313 195 XV.25

¹H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 7.90 (t, J = 8.8 Hz, 3H), 7.70(d, J = 8.8 Hz, 2H), 7.35 (m, 1H), 7.23- 7.21 (m, 1H), 7.19-7.15 (m,4H), 7.02 (d, J = 8.8 Hz, 2H), 6.82-6.76 (m, 4H), 3.63 (t, J = 7.4 Hz,2H), 1.53-1.51 (m, 2H), 1.35-1.31 (m, 2H), 0.86 (t, J = 7.3 Hz, 3H),LC-MS: m/z 480.2 (M + H)⁺ 314 196 XX.18

¹H NMR (400 MHz, DMSO-d6) δ 12.60 (bs, 1H), 8.37 (dd, J₁ = 2.0 Hz, J₂ =4.9 Hz, 1H), 7.81 (dd, J₁ = 1.9 Hz, J₂ = 7.8 Hz, 1H), 7.35 (d, J = 3.4Hz, 2H), 6.99-6.87 (m, 7H), 3.40 (s, 3H), 2.08 (s, 3H), 1.76 (s, 6H),1.69 (s, 6H). LC-MS: m/z 455.3 (M + H)⁺ 315 197 XV.26

¹H NMR (400 MHz, DMSO-d6) δ 13.6 (bs, 1H), 12.1 (s, 1H), 8.74 (d, J =8.3 Hz, 1H), 8.64 (s, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 8.4Hz, 2H), 7.63 (d, J = 7.3 Hz, 1H), 7.32 (d, J = 8.3 Hz, 2H), 7.17-7.05(m, 5H), 2.06 (bs, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC- MS: m/z 467.3(M + H)⁺ 316 198 XV.27

¹H NMR (400 MHz, DMSO-d6) δ 12.90 (bs, 1H), 10.10 (s, 1H), 8.55 (s, 1H),8.40 (s, 1H), 8.04 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 8.3 Hz, 2H), 7.64(d, J = 7.9 Hz, 1H), 7.44 (t, J = 7.9 Hz, 1H), 7.31 (d, J = 8.3 Hz, 2H),7.07 (d, J = 8.3 Hz, 2H), 7.02 (d, J = 5.4 Hz, 2H), 2.06 (s, 3H), 1.86(s, 6H), 1.73 (s, 6H). LC-MS: m/z 467.3 (M + H)⁺ 317 199 VI.51

¹H NMR (400 MHz, DMSO-d6) δ 13.80- 12.40 (s, 1H), 8.65 (s, 1H), 7.99 (d,J = 7.2 Hz, 1H), 7.89 (d, J = 7.2 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H),7.48 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.20-7.15 (m, 4H),3.99 (s, 3H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 478.2(M + H)⁺ 318 200 VI.52

¹H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 7.67 (d, J = 6.4 Hz, 1H),7.50-7.46 (m, 1H), 7.27 (d, J = 8.8 Hz, 2H), 7.20-7.17 (m, 2H), 6.80 (d,J = 8.8 Hz, 2H), 6.63 (d, J = 8.8 Hz, 2H), 6.37 (d, J = 8.4 Hz, 2H),5.03- 5.01 (m, 1H), 4.23-4.19 (m, 2H), 3.64-3.61 (m, 2H), 3.14 (s, 3H),2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 509.3 (M + H)⁺ 319201 XII.41

¹H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.04 (s, 1H), 7.78 (m, 1H),7.62 (d, J = 7.2 Hz, 3H), 7.34 (d, J = 6.4 Hz, 1H), 7.16 (d, J = 8.0 Hz,2H), 7.00-6.92 (m, 5H), 2.12 (m, 1H), 1.65 (s, 2H), 1.49-1.32 (m, 8H),1.17 (s, 2H), 0.85 (s, 6H). LC-MS: m/z 468.3 (M + H)⁺ 320 202 XII.42

¹H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 9.07 (s, 1H), 7.90 (s, 1H),7.64 (m, 3H), 7.36 (d, J = 6.8 Hz, 2H), 7.11 (t, J = 7.9 Hz, 2H), 7.00(m, 6H), 6.66 (m, 3H), 3.56 (m, 2H), 1.54 (m, 2H), 1.34 (m, 2H), 0.88(t, J = 7.3 Hz, 3H). LC-MS: m/z 453.3 (M + H)⁺ 321 203 XII.43

¹H NMR (400 MHz, DMSO-d6) δ 10.4 (bs, 1H), 7.59 (m, 1H), 7.47 (m, 3H),7.32 (d, J = 2.4 Hz, 2H), 6.96 (m, 4H), 2.05 (bs, 3H), 1.86 (s, 6H),1.76 (s, 6H). LC-MS: m/z 475.2 (M + H)⁺ 322 204 XII.44

¹H NMR (400 MHz, DMSO-d6) δ 13.50- 12.50 (bs, 2H), 8.72 (d, J = 2.0 Hz,2H), 8.11 (dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H),7.14-7.03 (m, 6H), 6.90 (d, J = 9.2 Hz, 2H), 3.27 (s, 3H), 2.05 (s, 3H),1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 493.4 323 205 VI.53

¹H NMR (400 MHz, DMSO-d6) δ 13.00- 12.80 (bs, 1H), 9.50-9.40 (bs, 1H),7.84 (d, J = 7.6 Hz, 1H), 7.8 (s, 1H), 7.3 (t, J = 8.0 Hz, 1H), 7.07-6.83 (m, 9H), 6.65 (t, J = 7.2 Hz, 1H), 3.47 (s, 2H), 1.98 (s, 3H),1.73-1.62 (m, 12H). LC-MS: m/z 469.2 (M + H)⁺ 324 206 XV.28

¹H NMR (400 MHz, DMSO-d6) δ 12.92 (s, 1H), 9.41 (s, 1H), 7.73- J = 7.6Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.8 Hz, 2H), 7.08 (d, J= 8.8 Hz, 2H), 7.0 (d, J = 8.4 Hz, 1H), 3.33 (s, 3H), 2.01 (s, 3H), 1.79(s, 6H), 1.69 (s, 6H). LC-MS: m/z 482.3 (M + H)⁺ 325 207 XX.19

¹H NMR (400 MHz, DMSO-d6) δ 13.85 (bs, 1H), 11.20 (bs, 1H), 8.46 (dd, J₁= 2.0 Hz, J₂ = 4.8 Hz, 1H), 8.31 (dd, J₁ = 1.6 Hz, J₂ = 7.6 Hz, 1H),7.94 (d, J = 8.8 Hz, 2H), 7.44 (dd, J = 8.8 Hz, 2H), 7.32 (d, J = 8.4Hz, 2H), 7.05- 6.98 (m, 3H), 3.09 (s, 3H), 2.04 (s, 3H), 1.84 (s, 6H),1.72 (s, 6H). LC-MS: m/z 518.3 (M + H)⁺ 326 208 XX.20

¹H NMR (400 MHz, DMSO-d6) δ 12.89 (bs, 1H), 7.71 (d, J = 7.6 Hz, 1H),7.55-7.51 (m, 1H), 7.26 (t, J = 7.6 Hz, 2H), 6.81-6.76 (m, 6H), 6.55 (d,J = 9.2 Hz, 2H), 3.50 (s, 2H), 3.16 (s, 3H), 3.05 (s, 3H), 1.97 (s, 3H),1.69-1.60 (m, 12H). LC-MS: m/z 497.3 (M + H)⁺ 327 209 VI.54

¹H NMR (400 MHz, DMSO-d6) δ 7.62-7.60 (m, 3H), 7.39-7.28 (m, 4H), 7.19(t, J = 7.2 Hz, 1H), 7.12-7.04 (m, 7H), 6.91 (d, J = 8.0 Hz, 2H),3.11-3.08 (m, 1H), 1.12 (d, J = 6.8 Hz, 6H). LC-MS: m/z 424.2 (M + H)⁺328 210 VI.55

¹H NMR (400 MHz, DMSO-d6) δ 14.00-13.20 (bs, 1H), 8.50 (s, 1H), 8.02 (d,J = 8.4 Hz, 1H), 7.92 (d, J = 7.2 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H),7.51-7.47 (m, 2H), 7.31-7.27 (m, 4H), 7.16 (d, J = 8.4 Hz, 2H), 3.96 (s,3H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 478.2 (M + H)⁺329 211 XV.29

¹H NMR (400 MHz, DMSO- d6) δ 10.80-10.20 (bs, 1H), 10.16 (s, 1H),7.98-7.94 (m, 3H), 7.84 (d, J = 8.4 Hz, 2H), 7.44-7.35 (m, 3H),7.33-7.24 (m, 3H), 7.21-7.20 (m, 3H), 7.13 (d, J = 7.2 Hz, 1H),6.90-6.86 (m, 1H), 3.07-3.01 (m, 1H), 1.13 (d, J = 7.2 Hz, 6H). LC-MS:m/z 451.2 (M + H)⁺ 330 212 XV.30

¹H NMR (400 MHz, DMSO-d6) δ 13.21 (s, 1H), 10.19 (s, 1H), 8.07 (t, J =7.8 Hz, 1H), 8.02 (d, J = 8.3 Hz, 2H), 7.85 (d, J = 7.4 Hz, 1H), 7.70(d, J = 8.3 Hz, 2H), 7.33 (m, 5H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s,6H). LC-MS: m/z 469.2 (M + H)⁺ 331 213

LC-MS: m/z 481.2 (M + H)⁺ 333 214 XV.31

¹H NMR (400 MHz, DMSO-d6) δ 13.17- 13.16 (bs, 1H), 10.17 (s, 1H), 9.77(s, 1H), 6.93 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H), 7.79 (s, 1H), 7.69 (d,J = 8.8 Hz, 2H), 7.63-7.62 (m, 1H), 7.49- 7.42 (m, 3H), 7.33-7.29 (m,3H), 6.85-6.81 (m, 1H), 2.06 (s, 3H), 1.83 (s, 6H), 1.70 (s, 6H). LC-MS:m/z 467.3 (M + H)⁺ 334 215 XV.32

¹H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 10.06 (s, 1H), 7.94 (d, J =8.3 Hz, 2H), 7.90 (d, J = 7.3 Hz, 1H), 7.68- 7.63 (m, 3H), 7.37 (t, J =6.8 Hz, 1H), 7.32 (d, J = 8.8 Hz, 2H), 7.16 (d, J = 8.3 Hz, 1H), 6.96(d, J = 8.3 Hz, 2H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS:m/z 468.1 (M + H)⁺ 335 216 XV.33

¹H NMR (400 MHz, DMSO-d6) δ 12.65 (bs, 1H), 9.91 (s, 1H), 7.93- 7.87 (m,3H), 7.68 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.29 (d, J =8.8 Hz, 2H), 7.22-7.16 (m, 3H), 6.74 (t, J = 7.6 Hz, 1H), 2.14-2.13 (m,1H), 1.69 (s, 2H), 1.53- 1.33 (m, 8H), 0.86 (s, 6H). LC-MS: m/z 495.3(M + H)⁺ 336 217

LC-MS: m/z 468.2 (M + H)⁺ 337 218 VI.56

¹H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 7.70 (d, J = 7.6 Hz, 1H),7.53 (t, J = 8.0 Hz, 1H), 7.26-7.19 (m, 4H), 6.92 (d, J = 8.8 Hz, 2H),6.85 (d, J = 8.8 Hz, 2H), 6.59 (d, J = 7.2 Hz, 2H), 3.20-3.19 (m, 4H),3.16 (s, 3H), 3.12-3.11 (m, 4H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s,6H). LC-MS: m/z 522.3 (M + H)⁺ 338 219 XII.45

¹H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.16 (s, 1H), 8.26 (s, 1H),7.73 (d, J = 8.4 Hz, 2H), 7.68-7.63 (m, 3H), 7.37 (d, J = 6.8 Hz, 1H),7.18 (s, 1H), 7.08 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.4 Hz, 1H), 6.91(d, J = 8.4 Hz, 2H), 2.05 (s, 9H), 1.65 (s, 6H). LC-MS: m/483.1z (M +H)⁺ 339 220 XII.46

¹H NMR (400 MHz, DMSO-d6) δ 12.0 (s, 1H), 9.81 (s, 1H), 7.86 (d, J = 7.6Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.8 Hz, 2H), 7.13- 7.01(m, 6H), 6.58 (t, J = 6.8 Hz, 1H), 2.83 (t, J = 7.6 Hz, 2H), 2.56 (t, J= 8.0 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z495.3 (M + H)⁺ 340 221 VI.57

¹H NMR (400 MHz, DMSO-d6) δ 13.0 (bs, 1H), 8.20 (bs, 1H), 7.70- 7.60 (m,1H), 7.60-7.50 (m, 1H), 7.35-7.31 (m, 2H), 7.23 (d, J = 8.4 Hz, 2H),7.10-6.97 (m, 4H), 6.71 (bs, 2H), 3.26 (s, 3H), 2.04 (s, 3H), 1.82 (s,6H), 1.72 (s, 6H). LC-MS: m/z 481.2 (M + H)⁺ 341 222 XV.35

¹H NMR (400 MHz, DMSO-d6) δ 13.10 (bs, 1H), 10.14 (s, 1H), 9.88 (bs,1H), 7.93 (d, J = 7.6 Hz, 1H), 7.79 (s, 1H), 7.68 (d, J = 8.8 Hz, 2H),7.61 (d, J = 7.6 Hz, 1H), 7.50-7.40 (m, 3H), 7.32- 7.29 (m, 3H), 6.82(t, J = 7.6 Hz, 1H), 2.14-2.10 (m, 1H), 1.68 (s, 2H), 1.53-1.43 (m, 8H),1.18 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 495.3 (M + H)⁺ 342 223 XVIII.3

¹H NMR (400 MHz, DMSO-d6) δ 13.8 (bs, 1H), 11.0 (bs, 1H), 8.84 (s, 1H),7.90 (d, J = 7.2 Hz, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.55-7.48 (m, 2H),7.43 (s, 1H), 7.33- 7.28 (m, 2H), 7.09 (t, J = 8.0 Hz, 1H), 6.82 (d, J =8.8 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 535(M + H)⁻ 343 224 XV.36

¹H NMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H), 7.94 (d, J = 7.6 Hz, 1H),7.84-7.80 (m, 3H), 7.62 (d, J = 7.6 Hz, 1H), 7.52-7.46 (m, 4H), 7.43-7.31 (m, 2H), 7.27-7.19 (m, 3H), 7.13 (d, J = 8.0 Hz, 1H), 6.82 (t, J =7.6 Hz, 1H), 3.05-3.01 (m, 1H), 1.13 (d, J = 6.8 Hz, 6H). LC-MS: m/z451.2 (M + H)⁺ 344 225 XV.37

¹H NMR (400 MHz, DMSO-d6) δ 14.00-13.8 (bs, 1H), 12.30 (s, 1H), 10.35(s, 1H), 8.71 (d, J = 8.0 Hz, 1H), 8.14-8.07 (m, 5H), 7.27-7.67 (m, 3H),7.35 (d, J = 8.0 Hz, 2H), 7.24 (t, J = 8.0 Hz, 1H), 2.06 (s, 3H), 1.87(s, 6H), 1.74 (s, 6H). LC- MS: m/z 495.1 (M + H)⁺ 345 226 XII.47

¹H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), 7.81 (d, J = 6.9 Hz, 1H),7.61 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7.8 Hz, 1H), 7.28 (d, J = 7.9 Hz,1H), 7.14 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 6.70 (d, J =8.3 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 4.25-4.19 (m, 1H), 3.13 (s, 3H),2.03 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H), 1.00 (d, J = 6.3 Hz, 6H).LC-MS: m/z 495.3 (M + H)⁺ 346 227 XV.38

¹H NMR (400 MHz, DMSO-d6) δ 13.10 (bs, 1H), 9.94 (s, 1H), 9.69 (s, 1H),8.01 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.78 (t, J = 7.6 Hz,1H), 7.70 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 7.2 Hz, 1H), 7.30 (d, J =8.4 Hz, 2H), 7.10 (d, J = 8.0 Hz, 1H), 2.15-2.13 (m, 1H), 1.69 (s, 2H),1.53-1.33 (m, 8H), 1.19 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 496.2 (M + H)⁺349 228 VI.58

¹H NMR (400 MHz, DMSO-d6) δ 15.33 (s, 1H), 8.63 (d, J = 8.3 Hz, 1H),8.04 (s, 1H), 7.99 (d, J = 7.3 Hz, 1H), 7.87 (d, J = 8.3 Hz, 2H), 7.58(s, 1H), 7.36 (s, 2H), 7.27 (t, J = 7.3 Hz, 1H), 6.96- 6.90 (m, 4H),2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 545.1 (M + H)⁻ 350229 VI.59

¹H NMR (400 MHz, DMSO-d6) δ 13.6 (bs, 1H), 12.02 (s, 1H), 8.73 (d, J =8.3 Hz, 1H), 8.30 (s, 1H), 8.04 (d, J = 6.8 Hz, 1H), 7.79 (d, J = 8.4Hz, 2H), 7.64 (d, J = 7.3 Hz, 1H), 7.44 (D, J = 1.5 Hz, 1H), 7.39-7.32(m, 2H), 7.16 (t, J = 7.8 Hz, 1H), 6.99 (d, J = 8.3 Hz, 2H), 2.07 (s,3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 501.1 (M + H)⁺ 353 230 XV.39

¹H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 10.02 (s, 1H), 7.80 (d, J =7.6 Hz, 1H), 7.66- 7.61 (m, 3H), 7.41-7.29 (m, 4H), 7.32-7.21 (m, 2H),7.09 (s, 1H), 6.62 (d, J = 7.2 Hz, 1H), 3.25 (s, 3H), 2.05 (s, 3H), 1.85(s, 6H), 1.73 (s, 6H). LC- MS: m/z 481.2 (M + H)⁺ 355 231 XX.21

¹H NMR (400 MHz, DMSO-d6) δ 13.01 (bs, 1H), 8.57 (d, J = 3.2 Hz, 1H),8.13-8.11 (m, 1H), 7.34-7.26 (m, 5H), 7.03 (d, J = 8.4 Hz, 2H), 6.80 (d,J = 8.8 Hz, 2H), 3.38 (s, 3H), 3.03 (s, 3H), 2.04 (s, 3H), 1.84 (s, 6H),1.72 (s, 6H). LC-MS: m/z 532.2 (M + H)⁺ 356 232

LC-MS: m/z 493.4 (M − H)⁺ 357 233 XX.22

¹H NMR (400 MHz, DMSO-d6) δ 7.42-7.38 (m, 2H), 7.17-7.15 (m, 1H), 7.11(t, J = 7.6 Hz, 2H), 7.03-7.01 (m, 3H), 6.87 (d, J = 8.8 Hz, 2H),6.71-6.69 (m, 1H), 6.51 (d, J = 9.2 Hz, 2H), 3.16 (s, 3H), 3.15 (s, 3H),2.04 (s, 9H), 1.64 (s, 6H). LC- MS: m/z 510.3 (M + H)⁺ 358 234 XII.49

¹H NMR (400 MHz, DMSO-d6) δ 13.68 (s, 1H), 10.58 (s, 1H), 10.19 (s, 1H),8.43 (dd, J₁ = 2.0 Hz, J₂ = 4.8 Hz, 1H), 8.28 (dd, J₁ = 1.7 Hz, J₂ = 7.6Hz, 1H), 8.14 (s, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.7 (d, J = 8.4 Hz,2H), 7.59 (d, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.33 (d, J =4.8 Hz, 2H), 6.92 (dd, J₁ = 4.8 Hz, J₂ = 7.6 Hz, 1H), 2.06 (s, 3H), 1.86(s, 6H), 1.74 (s, 6H). LC-MS: m/z 468.1 (M + H)⁺ 359 235 XII.50

¹H NMR (400 MHz, DMSO-d6) δ 12.85 (s, 1H), 10.12 (s, 1H), 8.57 (s, 1H),7.68-7.61 (m, 4H), 7.45-7.27 (m, 8H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73(s, 6H). LC-MS: m/z 465.1 (M − H)⁻ 360 236 XX.23

¹H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 7.78 (d, J = 7.9 Hz, 1H),7.60 (d, J = 7.8 Hz, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.37-7.31 (m, 3H),7.23-7.12 (m, 3H), 6.94 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.3 Hz, 1H),6.61 (d, J = 8.8 Hz, 2H), 3.17 (s, 3H), 2.97-2.91 (m, 1H), 1.09 (d, J =7.3 Hz, 6H), LC-MS: m/z 472.2 (M + H)⁺ 361 237 VI.60

¹H NMR (400 MHz, DMSO-d6) δ 13.75 (s, 1H), 12.15 (s, 1H), 8.69 (d, J =8.3 Hz, 1H), 8.05 (d, J = 8.3 Hz, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.65(t, J = 7.3 Hz, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.20 (t, J = 7.8 Hz, 1H),7.12 (d, J = 8.8 Hz, 2H), 7.07 (d, J = 8.3 Hz, 2H), 2.07 (s, 3H), 1.88(s, 6H), 1.74 (s, 6H). LC-MS: m/z 468.1 (M + H)⁺ 362 238 XX.24

¹H NMR (400 MHz, DMSO-d6) δ 12.76 (s, 1H), 7.41 (t, J = 8.3 Hz, 1H),7.12 (d, J = 8.8 Hz, 2H), 7.00 (d, J = 8.3 Hz, 1H), 6.91 (d, J = 8.4 Hz,2H), 6.76 (d, J = 7.8 Hz, 1H), 6.66 (d, J = 8.3 Hz, 2H), 6.60 (d, J =8.8 Hz, 2H), 3.82 (s, 3H), 3.13 (s, 3H), 3.09 (s, 3H), 2.02 (s, 3H),1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 497.3 (M + H)⁺ 363 239 XV.40

¹H NMR (400 MHz, DMSO-d6) δ 8.66 (d, J = 8.4 Hz, 1H), 8.29 (s, 1H), 8.02(dd, J₁ = 1.2 Hz, J₂ = 7.6 Hz, 2H), 7.65 (s, 1H), 7.44-7.32 (m, 3H),7.26 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 7.6 Hz, 1H), 7.10-7.04 (m, 2H),2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 467.3 (M + H)⁺ 364240 XV.41

¹H NMR (400 MHz, DMSO-d6) δ 10.4 (s, 1H), 8.4 (s, 1H), 8.26 (s, 1H),8.00 (d, J = 9.2 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.59 (s, 1H), 7.45(t, J = 7.6 Hz, 1H), 7.35-7.32 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H),7.21-7.19 (m, 1H), 7.08 (d, J = 8.8 Hz, 2H), 2.05 (s, 3H), 1.84 (s, 6H),1.73 (s, 6H). LC-MS: m/z 467.3 (M + H)⁺ 366 241 XII.53

¹H NMR (400 MHz, DMSO-d6) δ 13.69 (bs, 1H), 10.61 (s, 1H), 9.99 (s, 1H),8.42 (dd, J₁ = 1.0 Hz, J₂ = 4.8 Hz, 1H), 8.28 (dd, J₁ = 1.0 Hz, J₂ = 7.6Hz, 1H), 8.20 (s, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.67 (m, 1H), 7.54-7.46(m, 3H), 7.39-7.38 (m, 1H), 6.92 (dd, J₁ = 4.8 Hz, J₂ = 7.6 Hz, 1H),2.07 (s, 3H), 1.88 (d, J = 2.4 Hz, 6H), 1.71 (s, 6H). LC-MS: 502.2 (M +H)⁺ 367 242 XII.54

¹H NMR (400 MHz, DMSO-d6) δ 10.0 (s, 1H), 9.81-9.79 (bs, 1H), 7.93 (dd,J₁ = 1.2 Hz, J₂ = 7.6 Hz, 1H), 7.82 (s, 1H), 7.65-7.63 (m, 1H),7.51-7.43 (m, 5H), 7.38- 7.36 (m, 1H), 7.32 (d, J = 8.0 Hz, 1H),6.86-6.82 (m, 1H), 2.07 (s, 3H), 1.86 (d, J = 2.4 Hz, 6H), 1.74 (s, 6H).LC-MS: m/z 501.1 (M + H)⁺ 369 243

LC-MS: m/z 493.4 (M − H)⁺ 370 244 Com- pound 14

¹H NMR (400 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.45(d, J = 8.8 Hz, 1H), 7.53 (d, J = 3.2 Hz, 1H), 7.39 (d, J = 8.8 Hz, 2H),7.26 (d, J = 8.8 Hz, 2H), 7.19-7.14 (m, 3H), 7.11-7.07 (m, 3H), 6.63 (d,J = 2.4 Hz, 1H), 2.06 (s, 3H), 1.85 (d, J = 2.4 Hz, 6H), 1.73 (s, 6H).LC-MS: m/z 491.3 (M + H)⁺ 371 245 Com- pound 14

¹H NMR (400 MHz, DMSO-d6) δ 7.70-7.58 (m, 4H), 7.21-7.14 (m, 3H), 7.07(d, J = 8.0 Hz, 1H), 6.96 (d, J = 8.8 Hz, 2H), 6.89-6.84 (m, 5H), 6.35(d, J = 15.6 Hz, 1H), 2.04 (s, 3H), 1.86 (s, 6H), 1.72 (s, 6H). LC-MS:m/z 465.3 (M + H)⁺ 372 246 XVIII.4

¹H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 10.11 (s, 1H), 9.71 (bs,1H), 7.92 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H), 7.53 (s, 1H), 7.49-7.35(m, 4H), 7.23 (d, J = 8.4 Hz, 2H), 7.07-7.01 (m, 3H), 6.90 (t, J = 7.6Hz, 1H), 2.00 (s, 3H), 1.76 (s, 6H), 1.68 (s, 6H). LC-MS: m/z 503.2 (M +H)⁺ 373 247 XII.55

¹H NMR (400 MHz, DMSO-d6) δ 11.89 (s, 1H), 10.22 (s, 1H), 9.22 (s, 1H),8.36-8.28 (m, 2H), 7.7-7.51 (m, 4H), 7.33 (d, J = 8.0 Hz, 2H), 6.93 (s,1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 502.2 (M + H)⁺376 248 XII.57

¹H NMR (400 MHz, DMSO-d6) δ 13.00-12.8 (bs, 1H), 10.07 (s, 1H), 8.03(bs, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.56 (s, 1H), 7.41 (d, J = 8.0 Hz,1H), 7.36-7.26 (m, 4H), 7.21 (dd, J₁ = 0.8 Hz, J₂ = 7.6 Hz, 1H), 6.86(d, J = 8.0 Hz, 1H), 6.68 (d, J = 8.4 Hz, 1H), 3.79 (s, 3H), 2.06 (s,3H), 1.85 (d, J = 2.4 Hz, 6H), 1.73 (s, 6H). LC-MS: m/z 497.3 (M + H)⁺377 249 XII.58

¹H NMR (400 MHz, DMSO-d6) δ 12.16 (s, 1H), 9.12 (s, 1H), 7.99 (s, 1H),7.21 (d, J = 8.4 Hz, 2H), 7.08-6.98 (m, 6H), 6.07 (d, J = 2.4 Hz, 1H),6.0 (d, J = 2.4 Hz, 1H), 3.81 (s, 3H), 3.67 (s, 3H), 2.04 (s, 3H), 1.83(s, 6H), 1.72 (s, 6H). LC-MS: m/z 499.2 (M + H)⁺ 379 250 XII.59

¹H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.2 (bs, 1H), 7.39 (d, J =2.9 Hz, 1H), 7.22 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 6.3 Hz, 1H), 7.09(d, J = 5.8 Hz, 2H), 7.03 (dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 1H), 6.97 (d, J= 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 3.71 (s, 3H), 3.21 (s, 3H),2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 483.3 (M + H)⁺ 380251 XII.60

¹H NMR (400 MHz, DMSO-d6) δ 9.57 (s, 1H), 8.04 (s, 1H), 7.80 (d, J = 8.8Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.8 Hz, 2H), 7.06 (d, J= 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 6.41 (d, J = 2.0 Hz, 1H), 6.28(dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 2H), 3.69 (s, 3H), 2.06 (s, 3H), 1.83 (d,J = 2.0 Hz, 2H), 1.69 (s, 6H). LC-MS: m/z 469.3 (M + H)⁺ 381 252 XII.61

¹H NMR (400 MHz, DMSO-d6) δ 13.62 (bs, 1H), 10.36 (s, 1H), 8.36 (dd, J₁= 2.0 Hz, J₂ = 4.8 Hz, 1H), 8.24 (dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H),7.71- 7.67 (m, 2H), 7.49 (d, J = 2.0 Hz, 1H), 7.35 (dd, J₁ = 2.4 Hz, J₂= 8.8 Hz, JH), 6.98-6.93 (m, 3H), 6.85 (dd, J₁ = 4.8 Hz, H₂ = 7.6 Hz,1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.76 (s, 6H). LC-MS: m/z 475.2 (M + H)⁺383 253 XII.62

¹H NMR (400 MHz, DMSO-d6) δ 13.15 (bs, 1H), 9.65 (bs, 1H), 7.88 (dd, J₁= 1.6 Hz, J₂ = 8.0 Hz, 1H), 7.49 (d, J = 2.4 Hz, 1H), 7.37-7.33 (m, 2H),7.32 (d, J = 2.0 Hz, 2H), 7.09 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 8.8 Hz,1H), 6.94 (d, J = 8.8 Hz, 2H), 6.74 (t, J = 7.6 Hz, 1H), 2.14 (m, 1H),1.69 (s, 2H), 1.53-1.32 (m, 8H), 1.18 (s, 2H), 0.86 (s, 6H). LC-MS: m/z502.2 (M + H)⁺ 384 254 XII.63

¹H NMR (400 MHz, DMSO-d6) δ 11.20 (bs, 1H), 8.27-8.26 (m, 1H), 8.20 (dd,J₁ = 2.4 Hz, J₂ = 7.6 Hz, 1H), 7.72- 7.68 (m, 2H), 7.47 (d, J = 2.4 Hz,1H), 7.30 (dd, J₁ = 2.4 Hz, J₂ = 8.8 Hz, 1H), 6.94-6.92 (m, 3H),6.80-6.77 (m, 1H), 2.14- 2.13 (m, 1H), 1.68 (s, 2H), 1.52-1.23 (m, 8H),1.18 (s, 2H), 0.85 (s, 6H). LC-MS: m/z 503.3 (M + H)⁺ 385 255 VI.61

¹H NMR (400 MHz, DMSO-d6) δ 13.49 (s, 1H), 10.29 (s, 1H), 8.33 (s, 1H),8.21 (d, J = 6.4 Hz, 1H), 8.08-8.05 (bs, 1H), 7.60-7.52 (bs, 2H),7.22-6.46 (m, 12H), 3.60- 3.58 (bs, 2H), 1.60-1.54 (bs, 2H), 1.33 (bs,2H), 0.85 (t, J = 6.8 Hz, 3H). LC-MS: m/z 453.3 (M + H)⁺ 386 256 XV.44

¹H NMR (400 MHz, DMSO-d6) δ 13.5 (bs, 1H), 10.42 (bs, 1H), 8.31-8.26 (m,2H), 8.18 (d, J = 7.6 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.16- 7.06 (m,4H), 6.94 (d, J = 8.4 Hz, 2H), 6.77 (dd, J₁ = 4.8 Hz, J₂ = 7.6 Hz, 1H),3.27 (m, 6H), 1.84- 1.45 (m, 4H), 1.30-1.1 (m, 4H), 0.90-0.70 (m, 6H).LC-MS: m/z 461.3 (M + H)⁺ 387 257 XV.45

¹H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.50-8.40 (bs, 1H), 8.34-8.25(m, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.25 (s,1H), 7.13 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.84 (dd, J₁ =4.8 Hz, J₂ = 7.6 Hz, 1H), 2.06 (s, 9H), 1.65 (s, 6H). LC- MS: m/z 483.1(M + H)⁺ 388 258 VI.63

¹H NMR (400 MHz, DMSO-d6) δ 12.9 (s, 1H), 9.46 (s, 1H), 7.85 (dd, J₁ =1.6 Hz, J₂ = 8.4 Hz, 1H), 7.52 (s, 1H), 7.34-7.30 (m, 1H), 7.26- 7.18(m, 3H), 7.11 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 2.4 Hz, 1H), 7.00-6.97(m, 3H), 6.91-6.84 (m, 4H), 6.67 (t, J = 8.0 Hz, 1H), 3.62 (t, J = 7.2Hz, 2H), 1.58-1.50 (m, 2H), 1.38-1.29 (m, 2H), 0.88 (t, J = 7.6 Hz, 3H).LC-MS: m/z 486.2 (M + H)⁺ 389 259 VI.64

¹H NMR (400 MHz, DMSO-d6) δ 13.24 (s, 1H), 10.2 (s, 1H), 8.32 (s, 1H),8.22 (d, J = 7.6 Hz, 1H), 7.53 (bs, 2H), 7.22- 6.84 (m, 12H), 3.51 (bs,2H), 1.54 (s, 2H), 1.34- 1.23 (m, 2H), 0.88 (t, J = 6.8 Hz, 3H). LC-MS:m/z 487.2 (M + H)⁺ 392 260 XVIII.5

¹H NMR (400 MHz, DMSO-d6) δ 13.40- 13.20 (bs, 1H), 9.79 (s, 1H), 9.70(s, 1H), 7.95 (dd, J₁ = 1.2 Hz, J₂ = 8.0 Hz, 1H), 7.62 (d, J = 8.8 Hz,2H), 7.52-7.43 (m, 2H), 7.32-7.25 (m, 4H), 7.25-7.20 (m, 1H), 6.99-6.95(m, 1H), 2.02 (s, 3H), 1.79 (d, J = 2.4 Hz, 6H), 1.67 (s, 6H). LC-MS:m/z 537.2 (M + H)⁺ 393 261 XVIII.6

¹H NMR (400 MHz, DMSO-d6) δ 13.8 (bs, 1H), 10.85 (s, 1H), 9.71 (s, 1H),8.46 (dd, J₁ = 2.0 Hz, J₂ = 4.8 Hz, 1H), 8.31 (dd, J₁ = 1.6 Hz, J₂ = 7.6Hz, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.66 (d, J = 8.8 Hz, 2H), 7.30 (d, J= 2.0 Hz, 1H), 7.26 (dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz, 1H), 7.17 (d, J = 8.0Hz, 1H), 6.99 (dd, J₁ = 5.2 Hz, J₂ = 8.0 Hz, 1H), 2.02 (s, 3H), 1.79 (s,6H), 1.66 (s, 6H). LC-MS: m/z 538.0 (M + H)⁺ 394 262 XV.46

¹H NMR (400 MHz, DMSO-d6) δ 13.70 (bs, 1H), 10.80 (bs, 1H), 9.94 (s,1H), 8.40 (dd, J₁ = 2.0 Hz, J₂ = 4.8 Hz, 1H), 8.27 (dd, J₁ = 2.0 Hz, J₂= 7.6 Hz, 1H), 8.20 (s, 1H), 8.07 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 8.0Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.49-7.46 (m, 2H), 7.37 (dd, J₁ =2.0, J₂ = 8.4 Hz, 1H), 6.90 (dd, J₁ = 4.4 Hz, J₂ = 7.2 Hz, 1H), 2.16-2.15 (m, 1H), 1.71 (s, 2H), 1.56-1.34 (m, 8H), 1.20 (s, 2H), 0.87 (s,6H). LC-MS: m/z 503.2 (M + H)⁺ 395 263 XII.64

¹H NMR (400 MHz, DMSO-d6) δ 11.40-11.0 (bs, 1H), 10.17 (s, 1H), 7.92 (d,J = 7.2 Hz, 1H), 7.73-7.69 (m, 3H), 7.51 (d, J = 7.2 Hz, 1H), 7.45- 7.38(m, 2H), 7.29 (d, J = 2.4 Hz, 2H), 7.22-7.18 (m, 2H), 7.03 (d, J = 8.8Hz, 2H), 6.86-6.74 (m, 4H), 3.65 (t, J = 7.2 Hz, 2H), 1.56-1.53 (m, 2H),1.36-1.3 (m, 2H), 0.88 (t, J = 7.6 Hz, 3H). LC-MS: m/z 480.3 (M + H)⁺396 264 XVIII.7

¹H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), 9.80 (s, 1H), 9.73 (s, 1H),7.94 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H), 7.60 (d, J = 8.8 Hz, 2H),7.52-7.43 (m, 2H), 7.32-7.24 (m, 4H), 7.16 (d, J = 8.4 Hz, 1H), 6.97 (t,J = 7.6 Hz, 1H), 2.11-2.09 (m, 1H), 1.62 (s, 2H), 1.42-1.32 (m, 8H),1.15 (s, 2H), 0.83 (s, 6H), LC-MS: m/z 565.2 (M + H)⁺ 397 265 XVIII.8

¹H NMR (400 MHz, DMSO-d6) δ 13.80 (bs, 1H), 10.80 (s, 1H), 9.69 (s, 1H),8.46 (dd, J₁ = 1.6 Hz, J₂ = 4.4 Hz, 1H), 8.30 (dd, J₁ = 1.6 Hz, J₂ = 7.6Hz, 1H), 7.92 (d, J = 9.2 Hz, 2H), 7.65 (d, J = 8.8 Hz, 2H), 7.29 (d, J= 2.0 Hz, 1H), 7.25 (dd, J₁ = 2.0 Hz, J2 = 8.4 Hz, 1H), 7.16 (d, J = 8.4Hz, 1H), 6.99 (dd, J₁ = 4.8 Hz, J₂ = 7.6 Hz, 1H), 2.11-2.09 (m, 1H),1.62 (s, 2H), 1.46- 1.29 (m, 8H), 1.15 (s, 2H), 0.82 (s, 6H). LC- MS:m/z 566.2 (M + H)⁺ 398 266 XII.65

¹H NMR (400 MHz, DMSO-d6) δ 13.7 (s, 1H), 10.61 (s, 1H), 10.22 (s, 1H),8.43 (dd, J₁ = 2.0 Hz, J₂ = 4.8 Hz, 1H), 8.28 (dd, J₁ = 2.0 Hz, J₂ = 7.6Hz, 1H), 8.14 (s, 1H), 8.05 (s, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.52 (s,1H), 7.47 (s, 1H), 7.23-7.21 (m, 2H), 7.04 (d, J = 8.8 Hz, 2H),6.92-6.80 (m, 4H), 3.66 (t, J = 7.2 Hz, 2H), 1.57-1.53 (m, 2H),1.36-1.31 (m, 2H), 0.88 (t, J = 7.6 Hz, 3H). LC-MS: m/z 481.2 (M + H)⁺407 267 XV.47

¹H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 9.78 (s, 1H), 8.85 (t, J =5.8 Hz, 1H), 7.93 (dd, J₁ = 1.5 Hz, J₂ = 8.3 Hz, 1H), 7.87 (d, J = 8.3Hz, 2H), 7.49-7.40 (m, 2H), 7.32-7.23 (m, 6H), 6.89 (t, J = 6.9 Hz, 1H),4.43 (d, J = 5.9 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H).LC-MS: m/z 481.3 (M + H)⁺ 408 268 XV.48

¹H NMR (400 MHz, DMSO-d6) δ 12.00 (bs, 1H), 8.96 (t, J = 5.9 Hz, 1H),7.91 (d, J = 7.8 Hz, 1H), 7.64 (s, 1H), 7.38- 7.16 (m, 10H), 6.68 (t, J= 7.4 Hz, 1H), 4.41 (d, J = 5.9 Hz, 2H), 2.04 (s, 3H), 1.84 (s, 6H),1.72 (s, 6H). LC-MS: m/z 481.3 (M + H)⁺ 420 269 XII.66

¹H NMR (400 MHz, DMSO- d6) δ 13.2-13.0 (bs, 1H) 9.3- 9.0 (bs, 1H), 7.38(d, J = 2.8 Hz, 1H), 7.24-7.22 (m, 2H), 7.11-7.05 (m, 4H), 6.98-6.96 (m,2H), 6.89 (d, J = 9.2 Hz, 2H), 4.04-4.02 (m, 2H), 3.64-3.62 (m, 2H),3.21 (s, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 572.3(M + H)⁺ 453 35 XII.70

1H NMR (400 MHz, DMSO-d6): δ 13.10 (s, 1H), 9.12 (s, 1H), 7.37 (d, J =2.0 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 9.2 Hz, 2H), 7.05(dd, J1 = 2.8 Hz, J2 = 9.2 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.89 (d, J= 8.8 Hz, 2H), 3.68 (d, J = 6.4 Hz, 2H), 3.21 (s, 3H), 2.04 (s, 3H),2.01-1.98 (m, 1H), 1.83 (d, J = 2.6 Hz, 6H), 1.72 (s, 6H), 0.97 (d, J =6.8 Hz, 6H). LC-MS: m/z 525.3 (M + H)+ 473 36 Com- pound 20

1H-NMR (400 MHz, DMSO-d6): 12.67 (s, 1H), 10.01 (s, 1H), 9.57 (s, 1H),7.78 (d, J = 8.8 Hz, 1H), 7.43 (s, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.15(d, J = 8.4 Hz, 2H), 7.01-6.95 (m, 5H), 3.57 (t, J = 5.6 Hz, 2H), 3.24(s, 3H), 3.21 (s, 3H), 2.04 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS:m/z 554.3 (M + H)+ 521 37 XII.71

1H NMR (400 MHz, DMSO-d6): δ 13.20 (bs, 1H), 9.22 (bs, 1H), 7.46 (d, J =8.8 Hz, 2H), 7.41 (d, J = 2.8 Hz, 1H), 7.29 (d, J = 9.2 Hz, 1H), 7.23-7.09 (m, 5H), 6.81 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.27 (s, 3H).LC-MS: m/z 417.2 (M + H)+. 522 38 XII.72

1H NMR (400 MHz, DMSO-d6): δ 13.09 (bs, 1H), 9.08 (s, 1H), 7.35 (d, J =2.8 Hz, 1H), 7.10- 7.02 (m, 6H), 6.94 (d, J = 8.8 Hz, 2H), 6.85 (d, J =8.8 Hz, 2H), 3.69 (s, 3H), 3.18 (s, 3H), 2.42- 2.39 (m, 1H), 1.76-1.65(m, 5H), 1.38-1.20 (m, 5H). LC-MS: m/z 431.2 (M + H)+. 525 39 XII.73

1H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H), 7.26-7.12 (m, 5H), 6.99 (d, J =8 Hz, 2H), 6.88- 6.83 (m, 3H), 4.41 (s, 2H), 3.49-3.22 (m, 10H),2.10-2.07 (m, 7H), 1.89 (s, 5H), 1.79-1.75 (s, 6H). LC-MS: m/z 566.3(M + H)+. 526 40 XII.74

1H NMR (400 MHz, DMSO-d6): δ 7.46 (d, J = 2 Hz, 1H), 7.22 (d, J = 8.4Hz, 2H), 7.12-7.04 (m, 4H), 6.97 (d, J = 8 Hz, 2H), 6.88 (d, J = 8.4 Hz,2H), 4.13 (t, J = 5.2 Hz, 2H), 3.2 (s, 3H), 3.06 (s, 2H), 2.55 (s, 6H),2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 540.3 (M + H)+. 52741 XII.75

1H NMR (400 MHz, DMSO-d6): δ 13.18 (s, 1H), 9.25 (s, 1H), 7.61 (dd, J1 =2.4 & J2 = 7.6 Hz, 2H), 7.41 (d, J = 3.2 Hz, 1H), 7.30 (d, J = 9.2 Hz,1H), 7.23-7.16 (m, 4H), 7.09 (dd, J1 = 3.2 Hz, & J2 = 9.2 Hz, 1H), 6.73(d, J = 9.2 Hz, 2H), 3.74 (s, 3H), 3.27 (s, 3H). LC- MS: m/z 475.1 (M +H)+. 535 42 XII.76

1H NMR (400 MHz, DMSO-d6): δ 13.15 (s, 1H), 9.10 (s, 1H), 7.39 (d, J =3.2 Hz, 1H), 7.23- 7.16 (m, 5H), 7.11-7.07 (m, 3H), 6.81 (dd, J1 = 2.4Hz, & J2 = 6.8 Hz, 2H), 3.73 (s, 3H), 3.21 (s, 3H). LC-MS: m/z 382.84(M + H)+ 536 43 XII.77

1H NMR (400 MHz, DMSO-d6): δ 7.39 (d, J = 2.8 Hz, 1H), 7.08 (d, J = 8.4Hz, 5H), 7.03-7.02 (m, 1H), 6.95 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.0Hz, 2H), 4.02 (t, J = 4.0 Hz, 2H), 3.62 (t, J = 4.8 Hz, 2H), 3.30 (s,3H), 3.19 (s, 3H), 2.46-2.42 (m, 1H), 1.77-1.65 (m, 5H), 1.37-1.23 (m,5H). LC-MS: m/z 474.3 (M + H)+. 537 44 XII.78

1H NMR (400 MHz, DMSO-d6): δ 13.18 (bs, 1H), 8.95 (s, 1H), 7.37- 7.32(m, 3H), 7.22 (t, J = 9.2 Hz, 1H), 7.08-7.03 (m, 3H), 6.83-6.75 (m, 2H),6.66 (d, J = 8.4 Hz, 1H), 3.70 (s, 3H), 3.23 (s, 3H), 2.05 (s, 3H), 1.86(s, 6H), 1.73 (s, 6H). LC-MS: m/z 501.3 (M + H)+. 538 45 XII.79

1H NMR (400 MHz, DMSO-d6): δ 11.6-11.2 (bs, 1H), 7.47 (s, 1H), 7.09 (d,J = 8.8 Hz, 1H), 7.04-7.01 (m, 4H), 6.94 (d, J = 8.8 Hz, 2H), 6.81- 6.78(m, 1H), 6.74 (d, J = 8.4 Hz, 2H), 3.68 (s, 3H), 3.16 (s, 3H), 2.61-2.59 (m, 1H), 2.29 (s, 1H), 2.19 (s, 1H), 1.66- 1.65 (m, 1H), 1.58-1.51(m, 3H), 1.44 (d, J = 10 Hz, 1H), 1.31-1.21 (m, 2H), 1.11-1.09 (m, 1H).LC-MS: m/z 443.2 (M + H)+. 541 46 XII.80

1H NMR (400 MHz, DMSO-d6): δ 10.48 (s, 1H), 8.39 (dd, J1 = 2.0 Hz & J2 =4.8 Hz, 1H), 8.27 (dd, J1 = 2 Hz, & J2 = 8.0 Hz, 1H), 7.78 (d, J = 8.8Hz, 2H), 7.46 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 8.8 Hz, 2H), 6.90-6.87(m, 1H), 6.82 (d, J = 8.8 Hz, 2H), 3.29 (s, 3H). LC-MS: m/z 388.1 (M +H)+. 542 47 XII.81

1H NMR (400 MHz, DMSO-d6): δ 13.10- 12.90 (bs, 1H), 9.02 (s, 1H), 7.23(d, J = 2.0 Hz, 1H), 7.49 (dd, J1 = 2.0 Hz & J2 = 8.0 Hz, 1H), 7.40 (d,J = 8.8 Hz, 1H), 7.35 (d, J = 2.4 Hz, 2H), 7.05- 6.94 (m, 4H), 6.60 (d,J = 8.8 Hz, 2H), 3.70 (s, 3H), 3.19 (s, 3H). LC-MS: m/z 419.1 (M + H)+.543 48 XII.82

1H NMR (400 MHz, DMSO-d6): δ 13.1 (bs, 1H), 9.63 (s, 1H), 8.03 (d, J = 2Hz, 1H), 7.92- 7.90 (m, 1H), 7.69 (dd, J1 = 1.6 Hz, & J2 = 8.8 Hz, 1H),7.40-7.33 (m, 3H), 7.21-7.10 (m, 4H), 6.81- 6.77 (m, 1H). LC-MS: m/z 408(M + H)+. 544 49 XII.83

1H NMR (400 MHz, DMSO-d6): δ 13.22 (bs, 1H), 9.17 (s, 1H), 8.01 (d, J =2 Hz, 1H), 7.67 (dd, J1 = 1.6 Hz, & J2 = 8.8 Hz, 1H), 7.40 (d, J = 3.2Hz, 1H), 7.26-7.23 (m, 3H), 7.12-7.07 (m, 4H), 3.73 (s, 3H). LC-MS: m/z438.0 (M + H)+. 545 50 XII.84

1H NMR (400 MHz, DMSO-d6): δ 12.96 (bs, 1H), 8.97 (bs, 1H), 7.33 (d, J =2.8 Hz, 1H), 7.27 (t, J = 7.8 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 7.12(d, J = 8.0 Hz, 1H), 7.01- 6.96 (m, 4H), 6.89 (d, J = 8.8 Hz, 1H), 6.33(d, J = 8.8 Hz, 2H), 3.73 (s, 3H), 3.69 (s, 3H), 3.17 (s, 3H). LC-MS:m/z 379.2 (M + H)+. 546 51 XII.85

1H NMR (400 MHz, DMSO-d6): δ 13.03 (s, 1H), 9.54 (s, 1H), 7.88 (d, J = 8Hz, 1H), 7.42- 7.34 (m, 2H), 7.26-7.20 (m, 3H), 7.09 (d, J = 8.4 Hz,1H), 7.02 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 8 Hz, 2H), 6.74 (t, J = 7.2Hz, 1H), 1.80-1.67 (m, 5H), 1.44-1.11 (m, 6H). LC- MS: m/z 422.1 (M +H)+. 547 52 XII.86

1H NMR (400 MHz, DMSO-d6): δ 13.0 (s, 1H), 9.1 (s, 1H), 7.35 (d, J = 2.8Hz, 1H), 7.04-6.91 (m, 8H), 6.79 (d, J = 8.8 Hz, 2H), 3.74-3.70 (m, 7H),3.17 (s, 3H), 3.06- 3.04 (m, 4H). LC-MS: m/z 434.2 (M + H)+. 548 53XII.87

1H NMR (400 MHz, DMSO-d6): δ 13.2 (s, 1H), 9.2 (s, 1H), 7.39 (d, J = 3.2Hz, 1H), 7.24-7.09 (m, 8H), 6.84 (d, J = 8.8 Hz, 2H), 3.73 (s, 3H), 3.23(s, 3H). LC-MS: m/z 433.1 (M + H)+. 549 54 XII.88

1H NMR (400 MHz, DMSO-d6): δ 13.15 (bs, 1H), 8.94 (s, 1H), 7.37 (d, J =2.8 Hz, 1H), 7.24- 7.19 (m, 3H), 7.06-7.03 (m, 3H), 6.82-6.74 (m, 2H),6.64 (dd, J1 = 2 Hz, & J2 = 8.8 Hz, 1H), 3.70 (s, 3H), 3.23 (s, 3H),2.46- 2.42 (m, 1H), 1.80-1.68 (m, 5H), 1.40-1.21 (m, 5H). LC-MS: m/z449.2 (M + H)+. 550 55 XII.89

1H NMR (400 MHz, DMSO-d6): δ 13.1 (bs, 1H), 9.1 (bs, 1H), 7.39 (dd, J1 =2.8 & J2 = 9.2 Hz, 2H), 7.20-7.13 (m, 4H), 7.08-7.05 (m, 1H), 6.98-6.90(m, 3H), 3.72 (s, 3H), 1.79-1.67 (m, 5H), 1.40-1.33 (m, 5H), one protonmerged in DMSO. LC-MS: m/z 452.1 (M + H)+. 551 56 XII.90

1H NMR (400 MHz, DMSO-d6): δ 13.07 (bs, 1H), 8.95 (s, 1H), 7.27 (d, J =3.2 Hz, 1H), 7.23 (dd, J1 = 6.8 Hz & J2 = 8.8 Hz, 2H), 7.13 (d, J = 8.4Hz, 1H), 7.03 (dd, J1 = 3.2 Hz & J2 = 9.2 Hz, 1H), 6.94-6.89 (m, 3H),6.82- 6.76 (m, 2H), 3.70 (s, 3H), 3.21 (s, 3H), 3.21 (s, 3H), 1.98 (s,3H), 1.84 (s, 6H), 1.69 (s, 6H). LC-MS: m/z 497.3 (M + H)+. 552 57XII.91

1H NMR (400 MHz, DMSO-d6): δ 13.1 (s, 1H), 9.11 (s, 1H), 7.38 (d, J =2.8 Hz, 1H), 7.14- 7.05 (m, 6H), 6.98 (d, J = 8.8 Hz, 2H), 6.86 (d, J =8 Hz, 2H), 3.71 (s, 3H), 3.20 (s, 3H), 2.67- 2.59 (m, 1H), 2.08-1.83 (m,6H), 1.66-1.56 (m, 2H). LC-MS: m/z 467.2 (M + H)+. 553 58 XII.92

1H NMR (400 MHz, DMSO-d6): δ 13.06 (bs, 1H), 9.07 (bs, 1H), 7.37 (s,1H), 7.08-7.0 (m, 8H), 6.87 (d, J = 7.6 Hz, 2H), 4.70 (q, J = 8.8 Hz,2H), 3.71 (s, 3H), 3.19 (s, 3H). LC-MS: m/z 447 (M + H)+. 554 59 XII.93

1H NMR (400 MHz, DMSO-d6): δ 13.0 (bs, 1H), 9.1 (bs, 1H), 7.37 (d, J =2.8 Hz, 1H), 7.11- 7.06 (m, 6H), 6.95-6.85 (m, 4H), 3.71 (s, 3H), 3.19(s, 3H), 2.23 (s, 3H). LC-MS: m/z 363.1 (M + H)+. 555 60 XII.94

1H NMR (400 MHz, DMSO-d6): δ 13.2 (s, 1H), 11.73 (s, 1H), 9.1 (s, 1H),7.59 (brm, 2H), 7.40-7.12 (brm, 7H), 6.84 (brm, 2H), 3.73 (s, 3H),3.41-3.25 (brm, 7H), 2.01-1.77 (brm, 5H), 1.53 (brm, 1H). LC-MS: m/z432.4 (M + H)+. 556 61 XII.95

1H NMR (400 MHz, DMSO-d6): δ 13.1 (bs, 1H), 9.12 (bs, 1H), 7.37 (d, J =3.2 Hz, 1H), 7.13- 7.04 (m, 6H), 6.96 (d, J = 8.8 Hz, 2H), 6.89 (d, J =8.4 Hz, 2H), 3.71 (s, 3H), 3.45-3.41 (m, 1H), 3.20 (s, 3H), 2.25-2.22(m, 2H), 2.07-1.91 (m, 3H), 1.82-1.77 (m, 1H). LC-MS: m/z 403.2 (M +H)+. 557 62 XII.96

1H NMR (400 MHz, DMSO-d6): δ 13.15 (bs, 1H), 9.18 (bs, 1H), 7.39 (d, J =2.8 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.20- 7.14 (m, 3H), 7.10-7.05 (m,3H), 6.82 (d, J = 8.8 Hz, 2H), 5.87 (bs, 1H), 3.72 (s, 3H), 3.23 (s,3H), 2.73-2.61 (m, 4H), 2.18- 2.11 (m, 2H). LC-MS: m/z 465.2 (M + H)+.558 63 XII.97

1H NMR (400 MHz, DMSO-d6): δ 10.24 (bs, 1H), 8.32 (d, J = 2.8 Hz, 1H),8.21 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.8 Hz,2H), 6.98 (d, J = 8.8 Hz, 2H), 6.85-6.78 (m, 3H), 3.21 (s, 3H),2.40-2.32 (m, 1H), 1.78-1.67 (m, 5H), 1.37-1.23 (m, 5H). LC-MS: m/z402.3 (M + H)+. 560 64 XII.99

1H NMR (400 MHz, DMSO-d6): δ 13.04 (s, 1H), 8.94 (s, 1H), 7.37 (d, J =2.4 Hz, 1H), 7.13- 7.10 (m, 3H), 7.04-7.01 (m, 1H), 6.92-6.88 (m, 3H),6.81-6.75 (m, 2H), 3.70 (s, 3H), 3.21 (s, 3H), 2.42-2.40 (m, 1H), 2.12(s, 3H), 1.78-1.67 (m, 5H), 1.40-1.23 (m, 4H), 1.22 (s, 1H). LC-MS: m/z445.3 (M + H)+. 561 65 XII.100

1H NMR (400 MHz, DMSO-d6): δ 13.0 (s, 1H), 9.39 (s, 1H), 7.87 (dd, J1 =2 Hz & J2 = 8.0 Hz, 1H), 7.49 (d, J = 2.4 Hz, 1H), 7.36-7.26 (m, 3H),7.05 (d, J = 8.4 Hz, 1H), 6.97 (d, J = 2.4 Hz, 1H), 6.79-6.68 (m, 3H),2.16 (s, 3H), 1.69-1.18 (m, 13H), 0.85 (s, 6H). LC-MS: m/z 515.15 (M +H)+. 563 66 XII.101

1H NMR (400 MHz, DMSO-d6): δ 13.21 (s, 1H), 9.13 (s, 1H), 7.46 (d, J =8.8 Hz, 2H), 7.41 (d, J = 2.8 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.16(d, J = 2.4 Hz, 1H), 7.11- 7.04 (m, 3H), 6.83 (d, J = 8.8 Hz, 2H), 3.73(s, 3H), 3.28 (s, 3H), 2.21 (s, 3H). LC-MS: m/z 431.1 (M + H)+. 564 67XII.102

1H NMR (400 MHz, DMSO-d6) δ 13.1 (s, 1H), 9.0 (s, 1H), 7.48 (d, J = 2.4Hz, 1H), 7.33 (dd, J1 = 2.0 Hz, J2 = 2.4 Hz, 3H), 7.05-6.94 (m, 3H),6.81-6.73 (m, 2H), 3.71 (s, 3H), 2.14 (s, 3H), 1.69 (s, 2H), 1.52-1.18(m, 11H), 0.86-0.84 (m, 6H). LC-MS: m/z 547.2 (M + 2)+ 565 68 XII.103

1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.91 (s, 1H), 7.36 (d, J =2.8 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 7.05- 6.95 (m, 5H), 6.81 (s, 1H),6.71-6.68 (m, 2H), 4.74-4.67 (m, 2H), 3.69 (s, 3H), 3.20 (s, 3H), 2.09(s, 3H). LC-MS: m/z 461.2 (M + H)+. 566 69 XII.104

1H NMR (400 MHz, DMSO-d6) δ 13.06 (s, 1H), 9.45 (s, 1H), 8.03 (d, J =2.4 Hz, 1H), 7.89- 7.87 (m, 1H), 7.80 (dd, J1 = 2.4 Hz, J2 = 8.8 Hz,1H), 7.40-7.34 (m, 2H), 7.26-7.20 (m, 2H), 7.10 (d, J = 8.4 Hz, 1H),6.94 (d, J = 8.4 Hz, 1H), 6.76 (t, J = 7.2 Hz, 1H), 2.58- 2.52 (m, 1H),1.80-1.68 (m, 5H), 1.46-1.23 (m, 5H). LC-MS: m/z 423.1 (M + H)+. 567 70XIII.12

1H NMR (400 MHz, CDCl3): δ 7.55 (d, J = 3.2 Hz, 1H), 7.33 (d, J = 8.4Hz, 2H), 7.24 (s, 1H), 7.16-7.14 (m, 2H), 7.08- 7.06 (m, 2H), 7.03-7.0(m, 1H), 6.76 (d, J = 8.4 Hz, 2H), 4.07 (s, 2H), 3.80 (s, 3H), 3.5 (s,2H), 3.25 (s, 3H), 2.56 (s, 3H), 2.73 (s, 2H), 1.82 (s, 4H). LC-MS: m/z446.2 (M + H)+ 568 71 XII.106

1H NMR (400 MHz, DMSO-d6): δ 13.15 (s, 1H), 8.9 (s, 1H), 7.36 (d, J =2.8 Hz, 1H), 7.22-7.02 (m, 6H), 6.76 (d, J = 8.8 Hz, 1H), 6.67 (dd, J1 =2.4 Hz & J2 = 13.6 Hz, 1H), 6.54 (dd, J1 = 2.4 Hz & J2 = 8.8 Hz, 1H),4.75 (q, J = 8.8 Hz, 2H), 3.70 (s, 3H), 3.21 (s, 3H). LC-MS: m/z 465.1(M + H)+. 569 72 XII.107

1H NMR (400 MHz, DMSO-d6): δ 13.13 (s, 1H), 9.22 (s, 1H), 7.49- 7.45 (m,2H), 7.35 (d, J = 2.8 Hz, 1H), 7.27 (dd, J1 = 1.6 & J2 = 8, 1H), 7.15(d, J = 8.8 Hz, 1H), 7.08 (dd, J1 = 2.8 Hz & J2 = 9.2, 1H), 7.01-6.96(m, 2H), 6.68 (dd, J1 = 3.2 Hz & J2 = 10, 1H), 3.71 (s, 3H), 2.13 (s,1H), 1.66 (s, 2H), 1.5-1.3 (m, 8H), 1.17 (s, 2H), 0.88 (s, 6H). LC-MS:m/z 550.2 (M + H)+. 570 73 XII.107

1H NMR (400 MHz, DMSO-d6): δ 13.26 (s, 1H), 9.11 (s, 1H), 7.50 (d, J = 2Hz, 1H), 7.42- 7.34 (m, 3H), 7.11-7.06 (m, 2H), 7.01-6.94 (m, 2H), 6.72(d, J = 8.8 Hz, 1H), 3.72 (s, 3H), 2.14 (s, 1H), 1.69 (s, 2H), 1.53-1.33 (m, 8H), 1.23-1.18 (m, 2H), 0.86 (s, 6H). LC-MS: m/z 550.2 (M + H)+571 74 XII.108

1H NMR (400 MHz, DMSO-d6): δ 13.4 (bs, 1H), 9.14 (s, 1H), 7.62 (d, J =9.2 Hz, 2H), 7.42 (d, J = 2.4 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 7.18(d, J = 2 Hz, 1H), 7.12- 7.06 (m, 3H), 6.76 (d, J = 8.8 Hz, 2H), 3.74(s, 3H), 3.29 (s, 3H), 2.22 (s, 3H). LC-MS: m/z 489.1 (M + H)+. 572 75XII.109

1H NMR (400 MHz, DMSO-d6): δ 13.35 (s, 1H), 9.25 (s, 1H), 7.51 (d, J =8.8 Hz, 2H), 7.46- 7.41 (m, 2H), 7.23-7.11 (m, 3H), 7.03-7.01 (m, 1H),6.93 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.30 (s, 3H). LC-MS: m/z 435.1(M + H)+. 573 76 XII.110

1H NMR (400 MHz, DMSO-d6): δ 13.4 (bs, 1H), 9.27 (s, 1H), 7.65 (d, J =9.2 Hz, 2H), 7.48- 7.43 (m, 2H), 7.28-7.11 (m, 3H), 7.05 (d, J = 8.4 Hz,1H), 6.85 (d, J = 9.2 Hz, 2H), 3.75 (s, 3H), 3.30 (s, 3H). LC-MS: m/z493.1 (M + H)+. 574 77 XII.111

1H NMR (400 MHz, DMSO-d6): δ 13.30- 12.80 (bs, 1H), 9.11 (s, 1H), 7.37(d, J = 2.8 Hz, 1H), 7.15-7.07 (m, 6H), 6.98-6.95 (m, 2H), 6.90- 6.87(m, 2H), 3.71 (S, 3H), 3.21 (s, 3H), 1.91- 1.88 (m, 1H), 1.80-1.30 (m,9H), 1.0 (d, J = 6.8 Hz, 3H). LC-MS: m/z 445.3 (M + H)+. 575 78 XII.112

1H NMR (400 MHz, DMSO-d6): δ 13.2 (s, 1H), 9.2 (s, 1H), 7.8 (s, 1H),7.53 (d, J = 8.8 Hz, 1H), 7.40 (d, J = 2.8 Hz, 1H), 7.24-7.20 (m, 3H),7.16-6.88 (m, 5H), 3.73 (s, 3H). LC-MS: m/z 420.2 (M + H)+. 576 79XII.113

1H NMR (400 MHz, DMSO-d6) δ 13.24 (s, 1H), 9.20 (s, 1H), 8.46 (s, 1H),7.67 (dd, J1 = 2.0 Hz, J2 = 8.8 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.34(d, J = 8.8 Hz, 1H), 7.24 (m, 4H), 7.12 (dd, J1 = 3.6 Hz, J2 = 9.2 Hz,1H), 6.49 (d, J = 8.8 Hz, 1H), 3.74 (s, 3H), 3.41 (s, 3H). LC- MS: m/z471.66 (M + H)+ 577 80 XII.114

1H NMR (400 MHz, DMSO-d6) δ 13.1 (s, 1H), 8.90 (s, 1H), 7.37 (d, J = 3.6Hz, 1H), 7.11 (d, J = 8.4 Hz, 3H), 7.02 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz,1H), 6.92-6.88 (m, 3H), 6.81-6.75 (m, 2H), 3.70 (s, 3H), 3.21 (s, 3H),2.67-2.65 (m, 1H), 2.32- 2.31 (m, 1H), 2.22 (s, 1H), 2.11 (s, 3H), 1.71-1.40 (m, 4H), 1.40-1.11 (m, 4H). LC-MS: m/z 456.15 (M + H)+ 578 81XII.115

1H NMR (400 MHz, DMSO-d6) δ 13.30 (s, 1H), 9.18 (s, 1H), 7.98 (d, J =2.4 Hz, 1H), 7.56 (d, J = 10 Hz, 2H), 7.41 (d, J = 2.8 Hz, 1H), 7.30-7.17 (m, 5H), 7.13-7.10 (m, 1H), 3.74 (s, 3H), 3.30 (s, 3H), 1.25-1.21(m, 7H), 1.10 (s, 4H). LC-MS: m/z 432.3 (M + H)+ 579 82 XII.116

1H NMR (400 MHz, DMSO-d6) δ 13.45 (s, 1H), 9.61 (s, 1H), 8.09 (s, 1H),7.60-7.57 (m, 1H), 7.17 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.8 Hz, 1H),7.01 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 2.4 Hz, 1H), 6.77 (dd, J1 = 2.8Hz, J2 = 8.8 Hz, 1H), 6.68 (d, J = 9.2 Hz, 1H), 3.24 (s, 3H), 2.46-2.42(m, 1H), 2.09 (s, 3H), 1.80-1.68 (m, 5H), 1.43-1.23 (m, 5H). LC-MS: m/z481.10 (M + H)+. 580 83 XII.117

1H NMR (400 MHz, DMSO-d6) δ 13.38 (bs, 1H), 9.29 (s, 1H), 7.72 (s, 1H),7.33 (dd, J1 = 2.4 Hz, J2 = 9.6 Hz, 1H), 7.14 (t, J = 8.4 Hz, 3H), 6.98(d, J = 8.4 Hz, 2H), 6.91 (d, J = 1.6 Hz, 1H), 6.78 (dd, J1 = 1.6 Hz, J2= 8.0 Hz, 1H), 6.67 (d, J = 9.2 Hz, 1H), 3.23 (s, 3H), 2.46- 2.42 (m,1H), 2.10 (s, 3H), 1.79-1.68 (m, 5H), 1.39-1.20 (m, 5H). LC- MS: m/z498.15 (M + H)+ 581 84 XII.118

1H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1H), 9.20 (s, 1H), 7.85 (s, 1H),7.67 (s, 1H), 7.42 (d, J = 3.2 Hz, 1H), 7.35- 7.23 (m, 5H), 7.14-7.11(m, 1H), 6.70 (d, J = 6.70 Hz, 1H), 3.78 (s, 3H), 3.40 (s, 3H),1.78-1.72 (m, 6H), 1.38-1.32 (m, 5H). LC-MS: m/z 432.60 (M + H)+ 582 85XII.119

1H NMR (400 MHz, DMSO-d6) δ 9.2 (s, 1H), 7.38 (d, J = 3.2 Hz, 1H),7.15-7.07 (m, 6H), 6.99 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H3.72 (s, 3H), 3.48 (brm, 2H), 3.21 (s, 3H), 3.08-2.99 (brm, 2H), 2.77(s, 3H), 2.68 (brm, 1H), 2.0-1.8 (brm, 4H). LC-MS? m/z 445.24 (M + H)+.583 86 Com- pound 319

1H NMR (400 MHz, DMSO-d6) δ 13.12 (s, 1H), 9.10 (d, J = 5.2 Hz, 1H),7.37 (d, J = 3.2 Hz, 1H), 7.15-7.07 (m, 6H), 6.98-6.95 (m, 2H), 6.88 (d,J = 8.8 Hz, 2H), 3.71 (s, 3H), 3.21 (s, 3H), 2.46-2.44 (m, 1H), 1.91-1.88 (m, 1H), 1.72-1.45 (m, 8H), 1.00 (d, J = 7.2 Hz, 3H). LC-MS: m/z445.2 (M + H)+ 584 87 Com- pound 319

1H NMR (400 MHz, DMSO-d6) δ 13.20- 12.90 (bs, 1H), 9.21-8.95 (bs, 1H),7.37 (d, J = 2.8 Hz, 1H), 7.11-7.04 (m, 6H), 6.96 (d, J = 8.8 Hz, 2H),6.87 (d, J = 8.8 Hz, 2H), 3.71 (s, 3H), 3.20 (s, 3H), 2.40-2.32 (m, 1H),1.80-1.74 (m, 4H), 1.42- 1.35 (m, 3H), 1.10-0.95 (m, 2H), 0.90 (d, J =6.4 Hz, 3H). LC-MS: m/z 445.3 (M + H)+ 585 88 XII.120

1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 8.95 (s, 1H), 7.37 (d, J =3.6 Hz, 1H), 7.24- 7.18 (m, 3H), 7.06-7.03 (m, 3H), 6.82-6.74 (m, 2H),6.64 (dd, J1 = 2.0 Hz, J2 = 8.4 Hz, 1H), 3.70 (s, 3H), 3.21 (s, 3H),2.70- 2.67 (m, 1H), 2.33-2.26 (m, 2H), 1.72-1.69 (m, 1H), 1.62-1.42 (m,4H), 1.40-1.11 (m, 4H). LC- MS: m/z 461.2 (M + H)+ 586 89 XII.121

1H NMR (400 MHz, DMSO-d6) δ 13.3 (s, 1H), 10.55 (s, 1H), 9.50- 9.2 (brs,1H), 8.0 (d, J = 8.4 Hz, 2H), 7.71 (dd, J1 = 8.8 Hz, J2 = 12.8 Hz, 3H),7.52-7.51 (m, 1H), 7.47-7.33 (m, 4H), 7.14- 7.12 (m, 1H), 3.75 (s, 3H).LC-MS: m/z 431.1 (M + H)+ 587 90 XX.25

1H NMR (400 MHz, DMSO-d6) δ 12.5 (s, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.31(d, J = 2.8 Hz, 1H), 7.19-7.06 (m, 4H), 6.88 (d, J = 8.8 Hz, 2H), 6.77(d, J = 8.8 Hz, 2H) 3.79 (s, 3H), 3.25 (s, 3H). LC-MS: m/z 418.2 (M +H)+ 588 91 XII.123

1H NMR (400 MHz, DMSO-d6) δ 13.50- 12.90 (brs, 1H), 9.60- 9.10 (brs,1H), 7.42-7.32 (m, 5H), 7.23 (d, J = 8.8 Hz, 2H)), 7.12 (dd, J1 = 2.8Hz, J2 = 8.8 Hz, 1H), 3.75 (s, 3H), 3.42 (s, 3H). LC-MS: m/z 424.0 (M +H)+ 589 92 XII.124

1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.09 (brs, 1H), 7.4 (d, J =3.2 Hz, 1H), 7.32 (m, 1H), 7.25 (d, J = 8.8 Hz, 2H), 7.12-7.00 (m, 5H),6.86-6.82 (m, 1H), 3.70 (s, 3H), 3.26 (s, 3H). LC-MS: m/z 451.2 (M + H)+590 93 XII.125

1H NMR (400 MHz, DMSO-d6) δ 13.18 (s, 1H), 9.05 (s, 1H), 7.39 (d, J =3.2 Hz, 1H), 7.25- 7.19 (m, 3H), 7.08-7.05 (m, 2H), 6.98-6.86 (m, 4H),3.72 (s, 3H), 3.24 (s, 3H), 2.17 (s, 3H). LC-MS: m/z 447.2 (M + H)+ 59194 XII.126

1H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 9.08 (bs, 1H), 7.97 (d, J =2.8 Hz, 1H), 7.73 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 7.39-7.38 (m, 2H),7.24-7.17 (m, 2H), 7.07-6.99 (m, 3H), 3.71 (s, 3H), 2.57-2.52 (m, 1H),1.8-1.68 (m, 5H) 1.43-1.31 (m, 5H). LC- MS: m/z 453.2 (M + H)+ 592 95XII.127

1H NMR (400 MHz, DMSO-d6) δ 13.55- 12.95 (brs, 1H), 9.05 (s, 1H), 8.18(d, J = 2.4 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.54 (dd, J1 = 2.4 Hz, J2= 8.8 Hz, 1H), 7.39 (d, J = 2.8 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H),7.09-7.02 (m, 3H), 3.72 (s, 3H), 3.44 (s, 3H). LC-MS: m/z 481.2 (M + H)+593 96 XII.128

1H NMR (400 MHz, DMSO-d6) δ 13.11 (s, 1H), 9.20 (s, 1H), 7.37 (d, J =2.8 Hz, 1H), 7.14- 7.03 (m, 6H), 6.98-6.86 (m, 4H), 3.71 (s, 3H), 3.20(s, 3H), 2.33-2.32 (m, 1H), 1.58-1.42 (m, 6H), 1.33-1.29 (m, 2H),0.95-0.93 (m, 6H). LC- MS: m/z 459.3 (M + H)+ 594 97 XII.129

1H NMR (400 MHz, DMSO-d6) δ 13.2-13.0 (brs, 1H), 9.0-8.7 (bs, 1H), 8.29(s, 2H), 7.37 (d, J = 2.8 Hz, 1H), 7.23 (dd, J1 = 8.8 Hz, J2 = 11.6 Hz,4H), 6.99 (dd, J1 = 3.2 Hz, J2 = 9.6 Hz, 1H), 6.73 (d, J = 8.8 Hz, 1H),3.69 (s, 3H), 3.44 (s, 3H), 1.81-1.69 (m, 6H), 1.43- 1.35 (m, 5H) LC-MS:m/z 433.2 (M + H)+ 595 98 XII.130

1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 9.05 (bs, 1H), 8.18 (d, J =2.8 Hz, 1H), 7.79 (d, J = 9.2 Hz, 2H), 7.63 (dd, J1 = 2.8 Hz, J2 = 8.8Hz, 1H), 7.40 (t, J = 1.6 Hz, 1H), 7.29 (d, J = 8.8 Hz, 2H), 7.12 (d, J= 9.2 Hz, 1H), 7.09 (d, J = 1.6 Hz, 2H). 3.37 (s, 3H), 3.44 (s, 3H),LC-MS: m/z 476.1 (M + H)+. 596 99 XII.131

1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.0 (s, 1H), 8.09 (d, J = 2.4Hz, 1H), 7.44 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 7.39-7.37 (m, 5H),7.02 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H), 6.74(d, J = 9.6 Hz, 1H), 3.70 (s, 3H), 3.39 (s, 3H). LC-MS: m/z 434.1 (M +H)+ 597 100 XII.132

1H NMR (400 MHz, DMSO-d6) δ 9.2 (s, 1H), 7.42-7.38 (m, 3H), 7.33 (d, J =9.2 Hz, 1H) 7.22 (d, J = 8.8 Hz, 2H), 7.15- 7.12 (m, 1H), 6.39 (s, 1H),3.84 (s, 3H), 3.48 (s, 3H), 1.98-1.95 (m, 2H), 1.96-1.66 (m, 3H), 1.35-1.16 (m, 6H). LC-MS: m/z 438.2 (M + H)+ 598 101 XII.133

1H NMR (400 MHz, DMSO-d6) δ 13.60-12.80 (brs, 1H), 8.91 (s, 1H), 7.97(s, 1H), 7.60 (s, 1H), 7.38-7.27 (m, 5H), 7.05 (dd, J1 = 2.8 Hz, J2 =9.2 Hz, 1H), 6.87 (d, J = 9.2 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H), 3.71(s, 3H), 3.42 (s, 3H), 1.75-1.65 (m, 5H), 1.50-1.10 (m, 6H) LC-MS: m/z432.2 (M + H)+ 599 102 XII.134

1H NMR (400 MHz, DMSO-d6) δ 13.15 (bs, 1H), 8.92 (s, 1H), 7.94 (s, 1H),7.39-7.37 (m, 2H), 7.24-7.17 (m, 2H), 7.08 (s, 1H), 7.01 (dd, J1 = 3.2Hz, J2 = 9.2 Hz, 1H), 6.57 (d, J = 9.2 Hz, 1H), 3.69 (s, 3H), 2.57-2.53(m, 1H), 2.19 (s, 3H), 1.81- 1.68 (m, 5H), 1.43-1.33 (m, 5H). LC-MS: m/z467.1 (M + H)+ 600 103 XII.135

1H NMR (400 MHz, DMSO-d6) δ 13.10 (s, 1H), 9.06 (s, 1H), 8.00 (d, J =2.0 Hz, 1H), 7.77- 7.74 (m, 2H), 7.43 (s, 2H), 7.39 (s, 1H), 7.14 (d, J= 8.0 Hz, 1H), 7.04 (d, J = 9.2 Hz, 2H), 3.72 (s, 3H). LC-MS: m/z 455.0(M + H)+. 601 104 XII.136

1H NMR (400 MHz, DMSO-d6) δ 13.3 (s, 1H), 9.1 (s, 1H), 8.04- 8.01 (m,2H), 7.80-7.75 (m, 2H), 7.47 (d, J = 8.8 Hz, 1H), 7.40 (s, 1H),7.10-7.05 (m, 2H), 3.72 (s, 3H). LC-MS: m/z 439.5.1 (M + H)+ 602 105XII.137

1H NMR (400 MHz, DMSO-d6) δ 13.16 (s, 1H), 8.90 (s, 1H), 8.39 (s, 2H),7.71 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 3.2 Hz,1H), 7.06-7.02 (m, 1H), 6.87-6.83 (m, 1H), 3.71 (s, 3H), 3.55 (s, 3H).LC- MS: m/z 410.10 (M + H)+ 603 106 XII.138

1H NMR (400 MHz, DMSO-d6) δ 7.39 (d, J = 2.8 Hz, 2H), 7.13-7.09 (m, 6H),6.98 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.4 Hz, 2H), 3.71 (s, 3H), 3.20(s, 3H), 2.60-2.40 (m, 1H), 1.76-1.70 (m, 10H). LC-MS: m/z 498.25 (M +H)+ 609 107 XII.139

1H NMR (400 MHz, DMSO-d6) δ 13.00 (s, 1H), 8.74 (s, 1H), 7.97 (s, 1H),7.35 (d, J = 3.2 Hz, 1H), 7.27 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.4 Hz,2H), 6.99 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.49 (s, 1H), 6.44 (d, J =9.6 Hz, 1H), 3.69 (s, 3H), 3.36 (s, 3H), 1.96 (s, 3H), 1.81- 1.69 (m,5H), 1.43-1.23 (m, 6H). LC-MS: m/z 446.3 (M + H)+. 612 108 XII.140

1H NMR (400 MHz, DMSO-d6) δ 13.22 (s, 1H), 9.20 (s, 1H), 7.40 (d, J =2.8 Hz, 1H), 7.31 (d, J = 9.2 Hz, 1H), 7.23- 7.01 (m, 5H), 6.80 (s, 1H),6.61 (d, J = 1.2 Hz, 2H), 3.74 (s, 3H), 3.22 (s, 3H). LC-MS: m/z 417.1(M + H)+. 613 109 XII.141

1H NMR (400 MHz, DMSO-d6) δ 13.26 (s, 1H), 9.51 (s, 1H), 9.39 (s, 1H),7.79 (d, J = 2.0 Hz, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.33-7.21 (m, 6H),6.85 (d, J = 8.8 Hz, 2H), 3.30 (s, 3H), 2.91 (s, 3H). LC-MS: m/z 480.1(M + H)+. 614 110 XII.142

1H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), 9.70 (s, 1H), 8.25 (d, J =2.0 Hz, 1H), 7.62 (dd, J1 = 2.0 Hz, J2 = 8.8 Hz, 1H), 7.22-7.12 (m, 4H),7.02 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 2.4 Hz, 1H), 6.77 (dd, J1 = 2.4Hz, J2 = 8.4 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H), 3.25 (s, 3H), 2.37 (d, J= 5.2 Hz, 3H), 2.10 (s, 3H), 1.80- 1.68 (m, 5H), 1.40-1.23 (m, 6H).LC-MS: 508.2 (M + H)+. 615 111 XII.143

1H NMR (400 MHz, DMSO-d6) δ 13.24 (s, 1H), 9.08 (s, 1H), 8.24 (d, J =2.8 Hz, 1H), 8.03 (d, J = 2.8 Hz, 1H), 7.96- 7.93 (m, 1H), 7.80-7.77 (m,1H), 7.48 (d, J = 9.2 Hz, 1H), 7.40 (d, J = 2.0 Hz, 1H), 7.20 (d, J =8.4 Hz, 1H), 7.09-7.08 (m, 2H), 3.73 (s, 3H). LC-MS: m/z 497.0 (M + H)+.616 112 XII.144

1H NMR (400 MHz, DMSO-d6) δ 11.94-11.83 (bs, 1H), 8.41 (s, 2H), 7.50 (d,J = 2.4 Hz, 1H), 7.39 (s, 1H), 7.24 (s, 2H), 7.03 (d, J = 8.8 Hz, 1H),6.79-6.76 (m, 1H), 3.77 (s, 3H), 3.60-3.50 (m, 1H), 1.91-1.68 (m, 5H),1.51-1.22 (m, 5H), LC-MS: m/z 454.1 (M + H)+. 617 113 XII.145

1H NMR (400 MHz, DMSO-d6) δ 13.70- 12.80 (bs, 1H), 9.80-8.90 (bs, 1H),7.54-7.51 (m, 1H), 7.42 (d, J = 3.2 Hz, 1H), 7.32 (d, J = 9.2 Hz, 1H),7.25-7.09 (m, 5H), 6.81 (d, J = 2.4 Hz, 1H), 6.68-6.65 (m, 1H), 3.74 (s,3H), 3.28 (s, 3H). LC-MS: m/z 451.2 (M + H)+ 618 114 XII.146

1H NMR (400 MHz, DMSO-d6) δ 13.40- 12.80 (bs, 1H), 9.30-8.80 (bs, 1H),7.34 (d, J = 2.8 Hz, 1H), 7.08-6.95 (m, 4H), 6.60-6.58 (m, 2H), 5.89 (s,1H), 3.69 (s, 3H), 3.43 (s, 3H), 3.16 (s, 3H), 1.91-1.89 (m, 2H), 1.75-1.72 (m, 3H), 1.37-1.23 (m, 6H). LC-MS: m/z 435.2 (M + H)+ 619 115XII.147

1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.96 (s, 1H), 7.54 (d, J =2.8 Hz, 1H), 7.12- 7.08 (m, 3H), 7.05 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz,1H), 6.90-6.87 (m, 3H), 6.79-6.72 (m, 2H), 3.78- 3.72 (m, 1H), 3.19 (s,3H), 2.46-2.40 (m, 1H), 2.10 (s, 3H), 1.76-1.66 (m, 5H), 1.39-1.28 (m,5H), 0.72-0.70 (m, 2H), 0.69-0.66 (m, 2H). LC- MS: m/z 471.2 (M + H)+.620 116 XII.148

1H NMR (400 MHz, DMSO-d6) δ 8.67 (s, 1H), 7.14-7.04 (m, 4H), 6.92-6.88(m, 2H), 6.84- 6.75 (m, 5H), 3.84 (d, J = 10.4 Hz, 2H), 3.40- 3.34 (m,3H), 3.17 (s, 3H), 2.43-2.38 (m, 1H), 2.12 (s, 3H), 1.89-1.65 (m, 6H),1.35-1.17 (m, 8H). LC-MS: m/z 514.3 (M + H)+. 621 117 XII.149

1H NMR (400 MHz, DMSO-d6) δ 13.00- 12.90 (bs, 1H), 8.96 (s, 1H), 7.38(d, J = 2.8 Hz, 1H), 7.14-7.10 (m, 4H), 6.93-6.88 (m, 3H), 6.81- 6.77(m, 2H), 3.76-3.71 (m, 4H), 3.21 (s, 3H), 2.96-2.94 (m, 4H), 2.46- 2.39(m, 1H), 2.12 (s, 3H), 1.78-1.76 (m, 4H), 1.38-1.30 (m, 6H). LC-MS: m/z499.2 (M + H)+. 622 118 XII.150

1H NMR (400 MHz, DMSO-d6) δ 13.20 (s, 1H), 9.20 (s, 1H), 7.46- 7.41 (m,3H), 7.30 (d, J = 7.2 Hz, 1H), 7.23-7.10 (m, 5H), 6.77 (d, J = 8.8 Hz,2H), 3.74 (s, 3H), 3.27 (s, 3H), LC-MS: m/z 449.1 (M + H)+ 623 119XII.153

1H NMR (400 MHz, DMSO-d6) δ 13.00 (s, 1H), 9.30 (s, 1H), 7.33- 7.26 (m,3H), 7.05 (dd, J1 = 2.8 Hz, J2 = 9.2 Hz, 1H), 6.94-6.87 (m, 4H), 6.48(d, J = 8.8 Hz, 2H), 3.69 (s, 3H), 3.08 (s, 3H), 2.32-2.20 (m, 1H),1.86- 1.60 (m, 5H), 1.40-1.10 (m, 6H), 0.90-0.82 (m, 2H), 0.60-0.56 (m,2H). LC-MS: m/z 471.2 (M + H)+. 624 120 XII.151

1H NMR (400 MHz, DMSO-d6) δ 13.2-12.8 (bs, 1H), 9.40-8.80 (bs, 1H), 7.36(d, J = 1.6 Hz, 1H), 7.11 (d, J = 8.8 Hz, 2H), 7.03 (s, 2H), 6.68 (d, J= 8.8 Hz, 2H), 6.63 (s, 1H), 3.70 (s, 3H), 3.59 (s, 3H), 3.22 (s, 3H).LC- MS: m/z 421.2 (M + H)+ 625 121 XII.152

1H NMR (400 MHz, DMSO-d6) δ 13.26 (bs, 1H), 9.10 (s, 1H), 7.56 (dd, J1 =3.2 Hz, J2 = 9.6 Hz, 1H), 7.23-7.22 (m, 1H), 7.14-7.11 (m, 3H),6.96-6.91 (m, 3H), 6.79 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.69-6.65(m, 1H), 3.32 (s, 3H), 2.49- 2.43 (m, 1H), 2.10 (s, 3H), 1.79-1.67 (m,5H), 1.38-1.22 (m, 5H). LC- MS: m/z 433.2 (M + H)+. 626 122 XII.153

1H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 9.30 (s, 1H), 7.38- 7.36 (m,1H), 7.16 (d, J = 8.4 Hz, 1H), 7.09-7.02 (m, 3H), 6.95 (d, J = 9.2 Hz,1H), 6.84 (d, J = 8.4 Hz, 2H), 6.78 (dd, J1 = 2.8 Hz, J2 = 8.4 Hz, 1H),6.65 (d, J = 2.8 Hz, 1H), 3.71 (s, 3H), 3.19 (s, 3H), 2.49-2.43 (m, 1H),1.83- 1.67 (m, 6H), 1.37-1.21 (m, 5H), 0.86 (dd, J1 = 1.6 Hz, J2 = 8.0Hz, 2H), 0.57-0.53 (m, 2H). LC- MS: m/z 470.2 (M+)+. 627 123 XII.154

1H NMR (400 MHz, DMSO-d6) δ 8.79 (bs, 1H), 7.10-7.08 (m, 3H), 6.92-6.79(m, 6H), 6.64- 6.62 (m, 1H), 4.69 (s, 4H), 3.88 (s, 4H), 3.19 (s, 3H),2.46-2.40 (m, 1H), 2.11 (s, 3H), 1.78-1.67 (m, 5H), 1.37-1.29 (m, 5H).LC-MS: m/z 511.25 (M + H)+. 628 124 XII.155

1H NMR (400 MHz, DMSO-d6) δ 13.10- 13.00 (bs, 1H), 8.90-9.10 (bs, 1H),7.36 (d, J = 3.2 Hz, 1H), 7.14-7.10 (m, 3H), 7.02 (dd, J1 = 2.8 Hz, J2 =9.2 Hz, 1H), 6.93- 6.88 (m, 3H), 6.81-6.74 (m, 2H), 3.89 (t, J = 6.4 Hz,2H), 3.21 (s, 3H), 2.45-2.30 (m, 1H), 2.12 (s, 3H), 1.78-1.64 (m, 6H),1.43-1.33 (m, 8H), 0.94 (t, J = 4.4 Hz, 3H). LC-MS: m/z 486.2 (M + H)+.630 125 XII.156

1H NMR (400 MHz, DMSO-d6) δ 12.83 (bs, 1H), 9.12 (s, 1H), 7.59 (d, J =2.0 Hz, 1H), 7.12 (d, J = 8.8 Hz, 3H), 7.05 (dd, J1 = 2.0, J2 = 8.4 Hz,1H), 6.93-6.91 (m, 3H), 6.79 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H), 6.65(d, J = 8.0 Hz, 1H), 3.21 (s, 3H), 2.46-2.42 (m, 1H), 2.10 (s, 3H),1.92-1.67 (m, 6H), 1.41-1.33 (m, 5H), 0.86-0.82 (m, 2H), 0.54-0.51 (m,2H). LC-MS: m/z 455.3 (M + H)+. 631 126 XII.157

1H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 9.14 (s, 1H), 7.67 (d, J =1.6 Hz, 1H), 7.16 7.11 (m, 4H), 6.93-6.91 (m, 3H), 6.81-6.78 (m, 1H),6.67-6.64 (m, 1H), 3.22 (s, 3H), 2.43 (s, 1H), 2.20 (s, 3H), 2.11 (s,3H), 1.80-1.68 (m, 5H), 1.38- 1.23 (m, 5H). LC-MS: m/z 429.3 (M + H)+.632 127 XII.158

1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.60 (s, 1H), 8.42 (d, J =2.4 Hz, 1H), 8.24 (d, J = 4.8 Hz, 1H), 7.76 (dd, J1 = 2.0, J2 = 8.8 Hz,1H), 7.17-7.12 (m, 3H), 6.99 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 2.4 Hz,1H), 6.78 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.62 (d, J = 9.2 Hz, 1H),3.24 (s, 3H), 2.73 (d, J = 4.8 Hz, 3H), 2.46-2.44 (m, 1H), 2.10 (s, 3H),1.79-1.68 (m, 5H), 1.39-1.16 (m, 5H). LC-MS: m/z 472.4 (M + H)+. 633 128XII.159

1H NMR (400 MHz, DMSO-d6) δ 13.10- 13.00 (bs, 1H), 8.96 (s, 1H), 7.36(d, J = 3.2 Hz, 1H), 7.12 (dd, J1 = 4.4 Hz, J2 = 8.4 Hz, 3H), 7.04 (dd,J1 = 4.0 Hz, J2 = 9.2 Hz, 1H), 6.93-6.89 (m, 3H), 6.81-6.74 (m, 2H),3.48 (s, 2H), 3.21 (s, 3H), 2.33-2.32 (m, 1H), 2.12 (s, 3H), 1.79-1.68(m, 6H), 1.41-1.17 (m, 4H), 0.99 (s, 9H). LC-MS: m/z 501.4 (M+)+ 634 129XII.160

1H NMR (400 MHz, DMSO-d6) δ 13.10- 12.90 (bs, 1H), 8.95 (s, 1H), 7.38(d, J = 3.2 Hz, 1H), 7.12 (t, J = 8.0 Hz, 3H), 7.03 (dd, J1 = 2.8 Hz, J2= 8.8 Hz, 1H), 6.92- 6.89 (m, 3H), 6.80 (dd, J1 = 2.4 Hz, J2 = 8.0 Hz,1H), 6.74 (d, J = 8.8 Hz, 1H), 4.15-4.09 (m, 1H), 3.21 (s, 3H),2.45-2.38 (m, 1H), 2.12 (s, 3H), 1.89-1.86 (m, 2H), 1.79- 1.68 (m, 4H),1.55-1.24 (m, 14H). LC-MS: m/z 512.3 (M+)+. 635 130 XII.161

1H NMR (400 MHz, DMSO-d6) δ 13.1 (s, 1H), 9.35 (s, 1H), 8.15 (s, 3H),7.99 (d, J = 2.0 Hz, 1H), 7.41 (dd, J1 = 2.0 Hz, J2 = 8.8 Hz, 1H), 7.16-7.09 (m, 3H), 6.97 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 2.4 Hz, 1H), 6.79(dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.65 (d, J = 8.4 Hz, 1H), 3.92-3.87(m, 2H), 3.23 (s, 3H), 2.40 (s, 1H), 2.10 (s, 3H), 1.79-1.68 (m, 5H),1.39-1.22 (m, 5H). LC-MS: m/z 427.2 (M + H)+. 636 131 XII.162

1H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 7.61-7.59 (m, 1H), 7.38 (d, J= 8.4 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 7.11 (d, J = 8.8 Hz, 2H),6.91-6.88 (m, 3H), 6.80- 6.78 (m, 1H), 6.72 (d, J = 8.0 Hz, 1H), 3.21(s, 3H), 2.49-2.45 (m, 1H), 2.15 (s, 3H), 1.79-1.67 (m, 5H), 1.38-1.33(m, 5H). LC-MS: m/z 416.3 (M + H)+. 637 132 XII.163

1H NMR (400 MHz, DMSO-d6) δ 9.62-9.50 (bs, 1H), 8.90-8.70 (bs, 1H), 8.02(d, J = 1.2 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.16-7.10 (m, 3H),6.98-6.91 (m, 3H), 6.79 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.67 (d, J =8.8 Hz, 1H), 3.98 (s, 2H), 3.23 (s, 3H), 2.54 (s, 1H), 2.50 (s, 3H),2.10 (s, 3H), 1.79-1.68 (m, 5H), 1.39- 1.23 (m, 5H). LC-MS: m/z 456.3 (M− H)+. 638 133 XV.49

1H NMR (400 MHz, DMSO-d6) δ 13.00- 12.90 (bs, 1H), 10.12 (s, 1H), 8.57(s, 1H), 8.40 (t, J = 2.0 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.87 (d, J= 8.8 Hz, 2H), 7.63 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.17(d, J = 8.4 Hz, 2H), 7.11-7.05 (m, 4H), 2.46-2.42 (m, 1H), 1.81-1.78 (m,5H), 1.42-1.32 (m, 5H). LC-MS: m/z 415.2 (M + H)+. 640 134 XII.164

1H NMR (400 MHz, DMSO-d6) δ 8.09 (s, 1H), 7.18 (d, J = 8.4 Hz, 2H), 7.10(d, J = 8.4 Hz, 2H), 6.92 (d, J = 2.4 Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H),6.82-6.77 (m, 2H), 3.72 (s, 2H), 3.20 (s, 3H), 2.43 (s, 3H), 2.50 (s,3H), 2.14 (s, 3H), 1.78-1.67 (m, 5H), 1.40-1.32 (m, 5H). LC-MS: m/z470.3 (M + H)+. 641 135 XII.165

1H NMR (400 MHz, DMSO-d6) δ 8.38 (s, 1H), 7.68-7.64 (m, 1H), 7.37-7.31(m, 3H), 7.17- 7.03 (M, 6H), 6.78 (s, 1H), 2.46 (s, 1H), 1.79- 1.68 (m,5H), 1.39-1.16 (m, 5H). LC-MS: m/z 456.1 (M + H)+. 642 136 XII.166

1H NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1H), 8.57 (s, 1H), 8.20 (d, J =8.4 Hz, 1H), 7.82- 7.66 (m, 5H), 7.47 (d, J = 7.6 Hz, 1H), 7.21-7.17 (m,3H), 2.36 (s, 3H), 1.79-1.69 (m, 5H), 1.44- 1.21 (m, 6H). LC-MS: m/z430.2 (M + H)+. 643 137 XII.167

1H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 9.06 (s, 1H), 8.67 (d, J =2.0 Hz, 1H), 7.84 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 7.64 (t, J = 8.0Hz, 1H), 7.35 (d, J = 6.8 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.15 (d, J= 8.4 Hz, 2H), 6.91 (d, J = 8.4 Hz, 1H), 6.58 (d, J = 8.8 Hz, 1H), 3.34(s, 3H), 1.90-1.69 (m, 5H), 1.42- 1.22 (m, 6H). LC-MS: m/z 403.2 (M +H)+. 646 138 XII.168

1H NMR (400 MHz, DMSO-d6) δ 13.20- 12.40 (bs, 1H), 8.32 (s, 1H), 7.60(t, J = 8.0 Hz, 1H), 7.33-7.28 (m, 2H), 7.05-7.00 (m, 4H), 6.78 (d, J =2.4 Hz, 1H), 6.71- 6.67 (m, 2H), 4.75-4.68 (m, 2H), 3.20 (s, 3H), 2.13(s, 3H). LC-MS: m/z 432.2 (M + H)+. 647 139 XII.169

1H NMR (400 MHz, DMSO-d6) δ 8.42 (s, 1H), 7.66-7.60 (m, 2H), 7.35 (d, J= 6.4 Hz, 1H), 7.19 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 2.4 Hz, 1H),6.97-6.85 (m, 4H), 3.25 (s, 3H), 2.21 (s, 3H). LC- MS: m/z 418.05 (M +H)+ 648 140 XII.170

1H NMR (400 MHz, DMSO-d6) δ 9.43 (s, 1H), 7.91 (d, J = 9.2 Hz, 2H),7.74-7.70 (m, 1H), 7.46-7.43 (m, 3H), 7.17 (d, J = 8.8 Hz, 2H), 7.05 (d,J = 8.0 Hz, 1H), 6.78 (d, J = 8.8 Hz, 2H), 3.28 (s, 3H). LC-MS: m/z388.05 (M + H)+. 649 141 XII.171

1H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 10.21 (s, 1H), 8.40 (s, 1H),8.32 (s, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.45-7.39 (m, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.05 (d, J = 8.4 Hz, 2H), 6.88(d, J = 7.2 Hz, 2H), 2.36 (s, 3H), 1.79-1.68 (m, 5H), 1.39-1.23 (m, 6H).LC- MS: m/z 429.2 (M + H)+. 650 142 XII.172

1H NMR (400 MHz, DMSO-d6) δ 12.90 (s, 1H), 8.80 (s, 1H), 7.53- 7.50 (m,4H), 7.27 (d, J = 2.0 Hz, 1H), 7.18 (s, 1H), 7.13-7.11 (m, 1H), 7.01 (d,J = 8.4 Hz, 2H), 6.92 (d, J = 8.8 Hz, 1H), 3.75 (s, 3H), 2.03 (s, 3H),1.81-1.71 (m, 12H). LC- MS: m/z 506.3 (M + 2H)+. 651 143 XV.50

1H NMR (400 MHz, DMSO-d6) δ 13.0 (s, 1H), 10.1 (s, 1H), 8.39 (s, 1H),8.04 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 1.6 Hz, 1H), 7.72-7.69 (m, 1H),6.63 (d, J = 7.6 Hz, 1H), 7.55 (s, 1H), 7.46-7.44 (m, 1H), 7.16-7.11 (m,3H), 7.07 (d, J = 8.8 Hz, 2H), 2.52-2.46 (m, 1H), 2.29 (S, 3H),1.80-1.68 (m, 5H), 1.40-1.17 (m, 5H), LC-MS: m/z 427.2 (M + H)+. 652 144XII.173

1H NMR (400 MHz, DMSO-d6) δ 8.62 (s, 1H), 8.49 (s, 1H), 7.73- 7.69 (m,1H), 7.42 (d, J = 7.6 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.30 (d, J =8.4 Hz, 2H), 7.22-7.09 (m, 1H) 6.76 (s, 1H), 3.42 (s, 3H), 2.25 (s, 3H),1.85-1.70 (m, 5H), 1.45- 1.23 (m, 6H). LC-MS: m/z 417.2 (M + H)+. 654145 XII.174

1H NMR (400 MHz, DMSO-d6) δ 12.90 (s, 1H), 8.76 (s, 1H), 8.52 (d, J =2.4 Hz, 1H), 7.71- 7.68 (m, 1H), 7.51 (d, J = 9.2 Hz, 1H), 7.23-7.12 (m,4H), 6.87 (d, J = 9.2 Hz, 1H), 6.58 (d, J = 8.8 Hz, 1H), 3.74 (s, 3H),3.29 (s, 3H), 2.49-2.47 (m, 1H), 1.81-1.79 (m, 5H), 1.39-1.37 (m, 5H).LC-MS: m/z 431.3 (M − H)+. 655 146 XII.175

1H NMR (400 MHz, DMSO-d6) δ 7.70 (d, J = 2.4 Hz, 1H), 7.48-7.47 (m, 2H),7.37 (dd, J1 = 6.8 Hz, J2 = 7.6 Hz, 1H), 7.27-7.13 (m, 5H), 7.05- 7.03(m, 1H), 6.70 (d, J = 9.2 Hz, 1H), 3.38 (s, 3H), 2.48-2.47 (m, 1H),1.79-1.66 (m, 5H), 1.42- 1.10 (m, 6H). LC-MS: m/z 402.5 (M + H)+. 656147 XII.176

1H NMR (400 MHz, DMSO-d6) δ 8.02-7.60 (m, 2H), 7.14 (d, J = 8.4 Hz, 4H),6.97 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 2.4 Hz, 1H), 6.76-6.74 (m, 1H),6.40-6.30 (m, 1H), 3.22 (d, J = 8.8 Hz, 3H), 2.40 (s, 3H), 2.14 (s, 3H),1.89-1.72 (m, 5H), 1.42- 1.31 (m, 6H). LC-MS: m/z 509.2 (M + H)+. 659148 XII.177

1H NMR (400 MHz, DMSO-d6) δ 8.37 (bs, 1H), 7.65 (bs, 1H), 7.55 (t, J =8.0 Hz, 1H), 7.43 (d, J = 1.6 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.30-7.25 (m, 2H), 6.75 (d, J = 7.6 Hz, 1H), 6.19 (d, J = 8.8 Hz, 1H), 3.29(s, 3H), 2.45-2.41 (m, 1H), 1.84-1.69 (m, 5H), 1.45- 1.32 (m, 5H).LC-MS: m/z 437.2 (M + H)+. 660 149 XII.178

1H NMR (400 MHz, DMSO-d6) δ 10.75 (bs, 1H), 8.03 (s, 1H), 7.66 (t, J =8.0 Hz, 1H), 7.38-7.32 (m, 3H), 7.23-7.17 (m, 3H), 7.09 (d, J = 7.6 Hz,1H), 6.72 (s, 1H), 2.45- 2.41 (m, 1H), 1.79-1.67 (m, 5H), 1.43-1.30 (m,5H). LC-MS: m/z 490.1 (M + H)+. 661 150 XII.179

1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.25 (s, 1H), 7.49 (s, 1H),7.37-7.34 (m, 2H), 7.16 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H),6.75 (d, J = 8.4 Hz, 1H), 6.65 (s, 1H), 3.69 (s, 3H), 2.46-2.39 (m, 1H),1.79- 1.68 (m, 5H), 1.39-1.23 (m, 5H). LC-MS: m/z 486.2 (M + H)+. 662151 XII.180

1H NMR (400 MHz, DMSO-d6) δ 12.90 (s, 1H), 8.60 (s, 1H), 8.36 (s, 1H),7.69 (d, J = 2.0 Hz, 1H), 7.44-7.36 (m, 3H), 7.13 (d, J = 8.4 Hz, 2H),7.04 (d, J = 8.4 Hz, 2H), 6.98 (s, 1H), 6.66 (d, J = 14.0 Hz, 2H), 1.77-1.75 (m, 6H), 1.38-1.22 (m, 5H). LC-MS: m/z 469.1 (M + H)+. 663 152XII.181

1H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 7.62 (t, J = 9.6 Hz, 1H),7.32-7.24 (m, 3H), 7.17 (d, J = 8.0 Hz, 2H), 6.62 (d, J = 7.2 Hz, 1H),6.06 (s, 1H), 3.34 (s, 3H), 1.81-1.69 (m, 7H), 1.42- 1.23 (m, 5H),0.84-0.82 (bs, 2H), 0.44-0.43 (m, 2H). LC-MS: m/z 443.2 (M + H)+. 664153 XV.51

1H NMR (400 MHz, DMSO-d6) δ 13.20 (s, 1H), 10.14 (s, 1H), 9.90 (s, 1H),7.93 (d, J = 6.8 Hz, 1H), 7.78 (s, 1H), 7.66-7.60 (m, 3H), 7.50- 7.40(m, 3H), 7.30 (d, J = 4.0 Hz, 1H), 7.18 (d, J = 8.4 Hz, 2H), 6.83 (t, J= 7.2 Hz, 1H), 1.78-1.68 (m, 5H), 1.44-1.23 (m, 6H). LC-MS: m/z 415.2(M + H)+. 665 154 XII.182

1H NMR (400 MHz, DMSO-d6) δ 13.72 (bs, 1H), 10.60 (s, 1H), 9.95 (s, 1H),8.42 (d, J = 2.8 Hz, 1H), 8.29-8.27 (m, 1H), 8.20 (s, 1H), 8.07 ((d, J =8.4 Hz, 1H), 7.62 (d, J = 7.2 Hz, 1H), 7.50- 7.46 (m, 2H), 7.38 (s, 1H),7.24 (d, J = 8.4 Hz, 1H), 6.93-6.90 (m, 1H), 2.49-2.47 (m, 1H), 1.81-1.69 (m, 5H), 1.43-1.23 (m, 5H). LC-MS: m/z 450.1 (M + H)+. 666 155XII.183

1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 9.97 (s, 1H), 9.75 (s, 1H),7.93 (dd, J1 = 0.8 Hz, J2 = 7.6 Hz, 1H), 7.81 (s, 1H), 7.640 (d, J = 6.0Hz, 1H), 7.52-7.38 (m, 5H), 7.31 (d, J = 8.4 Hz, 1H), 7.24-7.22 (m, 1H),6.86- 6.82 (m, 1H), 2.49-2.43 (m, 1H), 1.81-1.68 (m, 5H) 1.46-1.22 (m,5H). LC-MS: m/z 449.05 (M + H)+. 669 156 XII.184

1H NMR (400 MHz, DMSO-d6) δ 13.25 (bs, 1H), 9.91 (s, 1H), 9.29 (bs, 1H),7.70 (s, 1H), 7.53 (d, J = 8 Hz, 1H), 7.47-7.32 (m, 6H), 7.23 (d, J = 8Hz, 1H), 7.12 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 3.74 (s, 3H),2.45-2.41 (m, 1H), 1.81- 1.68 (m, 5H), 1.46-1.31 (m, 5H). LC-MS: m/z479.2 (M + H)+. 671 157 XII.185

1H NMR (400 MHz, DMSO-d6) δ 13.40 (s, 1H), 9.61 (s, 1H), 8.23 (d, J =2.0 Hz, 1H), 7.60 (dd, J1 = 2.4 Hz, J2 = 9.2 Hz, 1H), 7.44 (s, 1H), 7.30(s, 2H), 7.21 (d, J = 6.5 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.60-6.50(m, 2H), 6.33 (dd, J1 = 2.8 Hz, J2 = 8.2 Hz, 1H), 3.19 (s, 3H), 2.36 (d,J = 4.8 Hz, 3H), 2.07 (s, 3H), 1.84-1.68 (m, 5H), 1.44- 1.16 (m, 6H).LC-MS: m/z 542.2 (M + H)+. 672 158 XII.186

1H NMR (400 MHz, DMSO-d6) δ 9.88 (s, 1H), 7.63 (dd, J1 = 2.8 Hz, J2 =6.8 Hz, 2H), 7.47 (d, J = 8 Hz, 1H), 7.41-7.33 (m, 3H), 7.29-7.21 (m,3H), 6.97 (d, J = 7.6 Hz, 1H), 3.80-3.75 (m, 1H), 2.45-2.41 (m, 1H),1.81- 1.68 (m, 5H), 1.46-1.32 (m, 5H), 0.74-0.73 (m, 2H), 0.64-0.60 (m,2H). LC-MS: m/z 505.2 (M + H)+. 673 159 XII.187

1H NMR (400 MHz, DMSO-d6) δ 8.75-9.00 (bs, 1H), 7.97 (s, 1H), 7.55 (d, J= 2.4 Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 7.00(dd, J1 = 2.4 Hz, J2 = 9.2 Hz, 1H), 6.49 (s, 1H), 6.43 (d, J = 9.2 Hz,1H), 3.78-3.71 (m, 1H), 3.35 (s, 3H), 2.45-2.41 (m, 1H), 1.97 (s, 3H),1.85-1.69 (m, 5H), 1.46- 1.32 (m, 5H), 0.75-0.70 (m, 2H), 0.65-0.58 (m,2H). LC-MS: m/z 472.25 (M + H)+. 675 160 XII.188

1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 7.80 (s, 1H), 7.53 (s, 1H),7.33-7.09 (m, 5H), 6.05 (s, 1H), 6.57 (d, J = 8.4 Hz, 1H), 3.63 (s, 3H),2.49-2.47 (m, 1H), 1.80-1.67 (m, 5H), 1.40- 1.33 (m, 5H). LC-MS: m/z518.1 (M + H)+. 676 161 XII.189

1H NMR (400 MHz, DMSO-d6) δ 12.92 (s, 1H), 8.58 (s, 1H), 8.02 (s, 1H),7.65 (s, 1H), 7.45- 7.29 (m, 5H), 7.17-7.15 (m, 1H), 6.80 (s, 1H), 6.67(s, 2H), 2.60-2.40 (m, 1H), 1.79-1.67 (m, 5H), 1.36-1.22 (m, 5H). LC-MS:m/z 489.2 (M + H)+. 677 162 XII.190

1H NMR (400 MHz, DMSO-d6) δ 13.60 (s, 1H), 10.48 (s, 1H), 8.34- 8.33 (m,1H), 8.22 (dd, J1 = 2.0 Hz, J2 = 8.0 Hz, 1H), 7.54 (s, 1H), 7.47 (s,1H), 7.29-7.20 (m, 2H), 7.15-7.09 (m, 3H), 6.83 (dd, J1 = 4.8 Hz, J2 =7.6 Hz, 1H), 6.65-6.63 (m, 1H), 2.49-2.45 (m, 1H), 1.77-1.67 (m, 5H),1.42- 1.18 (m, 5H). LC-MS: m/z 422.1 (M + H)+. 678 163 XII.191

1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.70 (s, 1H), 8.18 (d, J = 2.4Hz, 1H), 7.57 (dd, J1 = 2.4 Hz, J2 = 8.8 Hz, 1H), 7.17-7.12 (m, 3H),6.99 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 2.4 Hz, 1H), 6.78 (dd, J1 = 2.8Hz, J2 = 8.4 Hz, 1H), 6.60 (d, J = 8.8 Hz, 1H), 4.40 (bs, 4H), 3.90-3.80(m, 1H), 3.24 (s, 3H), 2.45-2.42 (m, 1H), 2.10 (s, 3H), 1.79-1.77 (m,5H), 1.39- 1.34 (m, 5H). LC-MS: m/z 523.3 (M + H)+ 679 164 XII.191

1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 9.61 (s, 1H), 8.19 (s, 1H),7.58 (dd, J1 = 1.6 Hz, J2 = 8.8 Hz, 1H), 7.47 (s, 1H), 7.17-7.12 (m,3H), 7.03-6.98 (m, 3H), 6.91 (s, 1H), 6.78 (dd, J1 = 2.2 Hz, J2 = 8.8Hz, 1H), 6.62 (d, J = 8.8 Hz, 1H), 4.39- 3.98 (m, 4H), 3.23 (s, 3H),2.49-2.43 (m, 1H), 2.10 (s, 3H), 1.79-1.68 (m, 6H), 1.42-1.30 (m, 5H).LC-MS: m/z 541.3 (M + H)+ 680 165 XII.192

1H NMR (400 MHz, DMSO-d6) δ 8.86 (s, 1H), 7.62-7.56 (m, 2H), 7.33-7.22(m, 3H), 7.11- 7.02 (m, 2H), 6.96 (d, J = 2.0 Hz, 1H), 6.88-6.83 (m,1H), 6.41 (d, J = 8.4 Hz, 1H), 2.47-2.42 (m, 1H), 2.09 (s, 3H), 1.81-1.66 (m, 5H), 1.42-1.22 (m, 5H). LC-MS: m/z 436.2 (M + H)+ 681 166XII.193

1H NMR (400 MHz, DMSO-d6) δ 8.25 (s, 1H), 7.56-7.54 (m, 1H), 7.41 (s,1H), 7.28-7.23 (m, 3H), 7.15-7.12 (m, 1H), 6.57-6.47 (m, 2H), 6.30 (d, J= 5.6 Hz, 1H), 3.17 (s, 3H), 2.04 (s, 3H), 1.86-1.66 (m, 5H), 1.44- 1.15(m, 6H). LC-MS: m/z 450.2 (M + H)+ 682 167 XII.194

1H NMR (400 MHz, DMSO-d6) δ 10.4 (s, 1H), 7.62-7.55 (m, 2H), 7.32-7.26(m, 4H), 7.16- 6.95 (m, 5H), 6.61 (d, J = 7.6 Hz, 1H), 2.44-2.32 (m,1H), 1.84-1.67 (m, 5H), 1.38-1.19 (m, 5H). LC-MS: m/z 422.0 (M + H)+

The below compounds were prepared by a procedure similar toIntermediate-XV using appropriate reactants and reagents and in presenceof suitable solvents and appropriate reaction conditions.

Com- pound CP No Reactant Structure Analytical data  72 277 Compound 24

LC-MS: m/z 466.1 (M + H)⁺  94 278 Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 14.55 (bs, 1H), 10.20 (bs, 1H), 8.72 (bs,1H), 7.68 (d, J = 8.8 Hz, 2H), 7.49 (s, 1H), 7.32 (d, J = 2.0 Hz, 1H),7.20-7.15 (m, 2H), 7.02 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H),1.72 (s, 6H). LC-MS: m/z 448.1 (M + H)⁺ 111 279 Compound 31

¹H NMR (400 MHz, DMSO-d6) δ 9.91 (s, 1H), 7.99 (s, 1H), 7.68 (dd, J₁ =1.6 Hz, J₂ = 8.0 Hz, 1H), 7.42 (s, 1H), 7.37 (s, 1H), 7.31 (d, J = 2.0Hz, 1H), 7.29-7.24 (m, 1H), 7.19-7.12 (m, 2H), 7.08-7.02 (m, 5H), 6.68(t, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS:m/z 472.2 (M + H)⁺ 112 280 Compound 279

¹H NMR (400 MHz, DMSO-d6) δ 8.45 (s, 1H), 8.14-8.12 (m, 2H), 7.74-7.70(m, 1H), 7.51 (t, J = 8.4 Hz, 1H), 7.43-7.38 (m, 4H), 7.33-7.29 (m, 1H),7.01 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.4 Hz, 1H), 2.06 (s, 3H), 1.87(s, 6H), 1.73 (s, 6H). LC-MS: m/z 482.1 (M + H)⁺ 120 281 Compound 31

¹H NMR (400 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.48 (m, 1H), 7.61 (dd, J₁ =1.6 Hz, J₂ = 8.0 Hz, 1H), 7.40 (s, 1H), 7.31 (d, J = 2.4 Hz, 1H), 7.26(t, J = 8.4 Hz, 1H), 7.19-7.01 (m, 7H), 6.74-6.70 (m, 1H), 3.29-3.24 (m,2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.12 (t, J = 7.2 Hz, 3H).LC-MS: m/z 500.2 (M + H)⁺ 123 282 Compound 31

¹H NMR (400 MHz, DMSO-d6) δ 7.41 (s, 1H), 7.29 (d, J = 2.0 Hz, 1H), 7.27(s, 1H), 7.24-7.21 (m, 1H), 7.18-7.13 (m, 2H), 7.10-7.03 (m, 2H), 6.99(s, 4H), 6.83 (t, J = 7.2 Hz, 1H), 2.91 (s, 6H), 2.04 (s, 3H), 1.82 (s,6H), 1.71 (s, 6H). LC-MS: m/z 500.4 (M + H)⁺ 164 283 Compound 31

¹H NMR (400 MHz, DMSO-d6) δ 9.62 (s, 1H), 8.45 (s, 1H), 7.59 (dd, J₁ =1.6 Hz, J₂ = 8.0 Hz, 1H), 7.40 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.26(t, J = 6.8 Hz, 1H), 7.20-7.02 (m, 7H), 6.72 (t, J = 7.6 Hz, 1H), 2.77(d, J = 5.2 Hz, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC- MS:m/z 485.2 (M + H)⁺ 208 284 Compound 92

¹H NMR (400 MHz, DMSO-d6) δ 9.0 (s, 1H), 7.6 (d, J = 7.3 Hz, 1H), 7.5(d, J = 8.9 Hz, 2H), 7.29 (d, J = 2.9 Hz, 1H), 7.26 (s, 1H), 7.15 (m,1H), 7.07-7.01 (m, 3H), 6.79 (t, J = 8.3 Hz, 2H), 2.98 (s, 6H), 2.04 (s,3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 501.3 (M + H)⁺ 209 285Compound 60

¹H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H), 8.15 (dd, J₁ = 2.0 Hz, J₂ =7.6 Hz, 1H), 7.55 (dd, J₁ = 2.0 Hz, J₂ = 7.6 Hz, 1H), 7.45 (d, J = 8.8Hz, 2H), 7.29 (s, 2H), 7.16 (dd, J₁ = 2.8 Hz, J₂ = 8.8 Hz, 1H), 7.07 (d,J = 8.4 Hz, 1H), 7.01 (d, J = 8.8 Hz, 2H), 6.78 (dd, J₁ = 4.8 Hz, J₂ =7.2 Hz, 1H), 2.97 (s, 6H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 501.3 (M + H)⁺ 605 168 Compound 279

1H NMR (400 MHz, DMSO-d6) δ 9.35 (s, 1H), 8.08 (s, 1H), 7.51 (bs, 1H),7.44 (d, J = 8.4 Hz, 2H), 7.30-7.27 (m, 2H), 7.12-7.00 (m, 5H), 6.77 (d,J = 8.8 Hz, 2H), 3.76 (s, 3H), 3.25 (s, 3H). LC- MS: m/z 416.10 (M +H)+. 606 169 Compound 279

1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 8.49-8.52 (m, 1H), 7.42 (d, J= 8.8 Hz, 2H), 7.28 (d, J = 8.8 Hz, 1H), 7.17 (d, J = 2.4 Hz, 1H),7.09-7.03 (m, 4H), 7.01-6.96 (m, 1H), 6.74 (d, J = 8.8 Hz, 2H), 3.75 (s,3H), 3.23 (s, 3H), 2.74 (d, J = 4.8 Hz, 3H). LC-MS: m/z 430.2 (M + H)+.607 170 Compound 279

1H NMR (400 MHz, DMSO-d6) δ 7.42 (d, J = 8.8 Hz, 3H), 7.22 (d, J = 8.8Hz, 1H), 7.00 (d, J = 8.4 Hz, 2H), 6.97-6.94 (m, 1H), 6.89 (d, J = 8.8Hz, 2H), 6.81 (d, J = 3.2 Hz, 1H), 6.72 (d, J = 8.8 Hz, 2H), 3.75 (s,3H), 3.22 (s, 3H), 2.90 (s, 3H), 2.81 (s, 3H). LC-MS: m/z 444.2 (M +H)+. 653 171 XI.53

1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.43 (d, J = 4.8 Hz, 1H), 7.83(d, J = 8.8 Hz, 1H), 7.22-7.14 (m, 3H), 6.97 (d, J = 8.4 Hz, 2H), 6.87(d, J = 2.0 Hz, 1H), 6.77-6.75 (m, 2H), 6.56-6.51 (m, 1H), 3.23 (s, 3H),2.73 (d, J = 4.8 Hz, 3H), 2.45 (d, J = 5.2 Hz, 3H), 2.14 (s, 3H),1.79-1.68 (m, 5H), 1.44-1.34 (m, 6H). LC-MS: m/z 522.2 (M + H)+

The below compounds were prepared by a procedure similar toIntermediate-XIV using appropriate reactants and reagents and inpresence of suitable solvents and appropriate reaction conditions.

Com- pound CP No Reactant Structure Analytical data 109 286 XV.4

¹H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 7.50 (d, J = 8.8 Hz, 2H), 7.41(s, 1H), 7.31 (s, 1H), 7.18 (m, 1H), 7.11 (s, 1H), 6.98 (d, J = 4.0 Hz,2H), 3.74 (m, 1H), 2.95 (t, J = 6.9 Hz, 2H), 2.08 (m, 4H), 1.90 (m, 7H),1.68 (m, 7H), 1.56-1.48 (m, 1H). LC- MS: m/z 450.2 (M + H)⁺ 230 287XV.10

¹H NMR (400 MHz, DMSO-d6) δ 9.88 (s, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.38(s, 1H), 7.30 (d, J = 2.0 Hz, 1H), 7.16-7.14 (m, 1H), 7.1 (d, J = 8.8Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s,6H), 1.17-1.15 (m, 2H), 0.87-0.84 (m, 2H). LC-MS: m/z 436.2 (M + H)⁺ 152288 Compound 77

¹H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 10.60 (bs, 1H), 8.48 (d, J =8.0 Hz, 1H), 8.08 (d, J = 2.8 Hz, 1H), 7.94 (dd, J₁ = 1.6 Hz, J₂ = 8.0Hz, 1H), 7.51-7.44 (m, 3H), 7.31 (d, J = 2.0 Hz, 1H), 7.16 (dd, J₁ = 1.6Hz, J₂ = 8.0 Hz, 1H), 6.98 (t, J = 8.4 Hz, 2H), 6.87 (t, J = 8.4 Hz,1H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.3 (M + H)⁺155 289 Compound 288

¹H NMR (400 MHz, DMSO-d6) δ 8.36 (d, J = 2.4 Hz, 1H), 8.26 (dd, J₁ = 1.2Hz, J₂ = 8.0 Hz, 1H), 8.07 (s, 1H), 7.88-7.84 (m, 1H), 7.75-7.70 (m,2H), 7.56 (d, J = 10 Hz, 1H), 7.51-7.47 (m, 1H), 7.43 (d, J = 2.0 Hz,1H), 7.32-7.26 (m, 2H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS:m/z 456.3 (M + H)⁺ 153 290 Compound 75

¹H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 10.46 (bs, 1H), 8.45 (s,1H), 8.14 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 8.8 Hz, 1H), 8.04 (s, 1H),7.94 (dd, J₁ = 1.6 Hz, J₂ = 8.0 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.47(t, J = 8.4 Hz, 1H), 7.35 (d, J = 2.4 Hz, 1H), 7.26 (dd, J₁ = 2.4 Hz, J₂= 8.8 Hz, 1H), 6.87 (t, J = 7.2 Hz, 1H), 2.05 (s, 3H), 1.85 (s, 6H),1.73 (s, 6H). LC-MS: m/z 475.5 (M + H)⁺ 154 291 Compound 74

¹H NMR (400 MHz, DMSO-d6) δ 13.43 (bs, 1H), 11.21 (bs, 1H), 8.82 (d, J =7.6 Hz, 1H), 8.44 (s, 2H), 8.0 (dd, J₁ = 2.0 Hz, J₂ = 8.4 Hz, 1H),7.60-7.54 (m, 2H), 7.32 (d, J = 2.0 Hz, 1H), 7.16 (dd, J₁ = 2.4 Hz, J₂ =8.8 Hz, 1H), 7.02-6.95 (m, 2H), 2.04 (s, 3H), 1.82-1.81 (bs, 6H), 1.72(s, 6H). LC-MS: m/z 475.2 (M + H)⁺ 175 292 VI.19

¹H NMR (400 MHz, DMSO-d6) δ 13.65 (bs, 1H), 10.95 (bs, 1H), 8.42 (s,2H), 8.29 (dd, J₁ = 2.0 Hz, J₂ = 8.0 Hz, 1H), 8.10 (d, J = 3.2 Hz, 1H),7.54 (m, 2H), 7.32 (d, J = 2.0 Hz, 1H), 7.16 (dd, J₁ = 2.0 Hz, J₂ = 8.4Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 6.92 (dd, J₁ = 5.2 Hz, J₂ = 8.0 Hz,1H), 2.08 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M + H)⁺540 172 IX.5

1H NMR (400 MHz, DMSO-d6): δ 13.38 (s, 1H), 10.75 (s, 1H), 8.36 (d, J =8.4 Hz, 1H), 8.26 (d, J = 1.6 Hz, 1H), 8.05 (d, J = 1.2 Hz, 1H), 7.97(dd, J₁ = 1.6 Hz & J₂ = 8.0 Hz, 1H), 7.55-7.51 (m, 1H), 7.49 (d, J = 2.4Hz, 1H), 7.38-7.35 (m, 1H), 7.22 (d, J = 8.8 Hz, 1H), 6.97 (t, J = 8 Hz,1H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H), LC-MS: m/z 476.2 (M + H)+559 173 XII.98

1H NMR (400 MHz, DMSO-d6): δ 13.38 (bs, 1H), 11.05 (bs, 1H), 8.36 (d, J= 8.8 Hz, 1H), 8.24 (s, 1H), 8.02 (s, 1H), 7.97 (d, J = 6.8 Hz, 1H),7.50 (t, J = 7.6 Hz, 1H), 7.41 (d, J = 1.6 Hz, 1H), 7.24-7.17 (m, 2H),6.95 (t, J = 7.2 Hz, 1H), 2.58-2.52 (m, 1H), 1.81-1.68 (m, 5H),1.42-1.31 (m, 5H). LC-MS: m/z 424.2 (M + H)+.

Synthesis of2-((4-(4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)amino)phenyl)carbamoyl)benzoic acid (Compound-293) (CP-119)

Step (i): A solution of Intermediate-XI (0.05 g, 0.16 mmol, 1 eq.) andphthalic anhydride (0.024 g, 0.16 mmol, 1 eq.) in DCM was stirred at RTfor 2 h. The precipitate obtained was filtered and dried in vacuo toafford title product as pale-yellow solid (0.01 g, 12.50%).

¹H NMR (400 MHz, DMSO-d6) δ12.98 (s, 1H), 10.17 (s, 1H), 7.86 (d, J=7.8Hz, 1H), 7.63 (d, J=7.3 Hz, 1H), 7.57-7.52 (m, 4H), 7.41 (s, 1H), 7.31(d, J=1.6 Hz, 1H), 7.17-7.12 (m, 2H), 7.04 (d, J=8.8 Hz, 2H), 2.05 (s,3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 501.1 (M+H)⁺²

The below compounds were prepared by a procedure similar to Compound 293using appropriate reactants and reagents and in presence of suitablesolvents and appropriate reaction conditions.

Compound CP No Reactant Structure Analytical data  90 294 Int-I.1

¹H NMR (400 MHz, DMSO-d6) δ 11.80 (bs, 1H), 9.75 (s, 1H), 7.47 (d, J =8.8 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H), 3.12-3.08 (m, 1H), 2.93-2.91 (m,1H), 2.00-1.92 (m, 4H), 1.91-1.75 (m, 16H), 1.72-1.54 (m, 1H). LC-MS:m/z 368.1 (M + H)⁺  96 295 Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 11.9 (bs, 1H), 9.71 (bs, 1H), 7.43 (d, J =8.8 Hz, 2H), 7.33 (s, 1H), 7.30 (d, J = 2.5 Hz, 1H), 7.16-7.14 (m, 1H),7.08 (m, 1H), 6.97 (d, J = 8.8 Hz, 2H), 3.12-3.08 (m, 1H), 2.94-2.90 (m,1H), 2.04 (s, 4H), 1.99-1.82 (m, 10H), 1.71 (m, 7H). LC-MS: m/z 493.3(M + H)⁺ 105 296 Int-I.1

¹H NMR (400 MHz, DMSO-d6) δ 7.52 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 8.4Hz, 2H), 2.72 (t, J = 7.2 Hz, 2H), 2.67-2.63 (m, 2H), 2.05 (s, 3H), 1.79(d, J = 7.6 Hz, 8H), 1.69 (s, 6H). LC-MS: m/z 366.1 (M + H)⁺ 110 297Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 12.9 (bs, 1H), 10.06 (s, 1H), 7.47 (d, J =8.8 Hz, 2H), 7.42 (s, 1H), 7.30 (d, J = 2.0 Hz, 1H), 7.17-7.10 (m, 2H),6.98 (d, J = 8.8 Hz, 2H), 2.76 (t, J = 7.6 Hz, 2H), 2.74-2.62 (m, 2H),2.03 (s, 3H), 1.90-1.86 (m, 2H), 1.81-1.80 (bs, 6H), 1.71 (s, 6H).LC-MS: m/z 491.1 (M + H)⁺ 132 298 XI.2

¹H NMR (400 MHz, DMSO-d6) δ 11.83 (s, 1H), 9.74 (s, 1H), 7.54 (s, 1H),7.5 (d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.28-7.15 (m, 4H), 7.13 (s, 2H),7.09 (d, J = 8.8 Hz, 2H), 3.13-3.09 (m, 1H), 2.96-2.90 (m, 1H), 2.25 (s,3H), 2.04-1.77 (m, 4H). LC-MS: m/z 449.1 (M + H)⁺ 133 299 XI.2

¹H NMR (400 MHz, DMSO-d6) δ 12.85 (bs, 1H), 10.15 (s, 1H), 7.62 (s, 1H),7.55 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 2.0 Hz, 1H), 7.29-7.11 (m, 8H),2.80-2.76 (m, 2H), 2.65-2.63 (m, 2H), 2.26 (s, 3H), 1.94-1.88 (m, 2H).LC-MS: m/z 447.1 (M + H)⁺ 176 300 Int-XI

¹H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 10.42 (bs, 1H), 7.46 (d, J =8.8 Hz, 2H), 7.42 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.16 (m, 1H), 7.12(m, 1H), 6.98 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s,6H), 1.41 (s, 4H). LC-MS: m/z 465.3 (M + H)⁺ 216 301 XI.1

¹H NMR (400 MHz, DMSO-d6) δ 14.8 (bs, 1H), 8.04 (s, 1H), 7.46 (s, 1H),7.41 (s, 1H), 7.30 (s, 2H), 7.19 (s, 1H), 6.82 (s, 1H), 2.06 (s, 3H),1.86 (d, J = 2.4 Hz, 6H), 1.63 (s, 6H), 1.19 (d, J = 5.6 Hz, 2H), 1.10(d, J = 5.6 Hz, 2H). LC-MS: m/z 533.2 (M + H)⁺ 229 302 Compound 300

¹H NMR (400 MHz, DMSO-d6) δ 10.56 (s, 1H), 7.82 (d, J = 4.4 Hz, 1H),7.47-7.42 (m, 3H), 7.31 (d, J = 2.0 Hz, 1H), 7.19-7.16 (m, 1H), 7.11 (d,J = 8.4 Hz, 1H), 6.98 (d, J = 8.8 Hz, 2H), 2.62 (d, J = 4.4 Hz, 3H),2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.36-1.29 (m, 4H). LC-MS: m/z478.3 (M + H)⁺ 237 303 XI.7

¹H NMR (400 MHz, DMSO-d6) δ 7.53 (s, 1H), 7.34 (d, J = 2.0 Hz, 1H), 7.30(s, 1H), 7.25-7.22 (m, 2H), 7.11 (t, J = 7.6 Hz, 1H), 7.03 (d, J = 8.0Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s,6H), 1.34-1.24 (m, 4H). LC-MS: m/z 465.2 (M + H)⁺ 239 304 VI.37

¹H NMR (400 MHz, DMSO-d6) δ 12.4 (bs, 1H), 7.7 (s, 1H), 7.36 (s, 1H),7.23 (s, 2H), 7.14 (d, J = 7.8 Hz, 2H), 6.95 (d, J = 8.3 Hz, 2H), 3.13(s, 3H), 2.08 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.17 (m, 2H), 0.85(m, 2H). LC-MS: m/z 479.2 (M + H)⁺ 348 305 XI.30

¹H NMR (400 MHz, DMSO-d6) δ 12.85 (bs, 1H), 10.11 (bs, 1H), 7.91 (s,1H), 7.85 (d, J = 8.0 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.57-7.52 (m,4H), 7.19 (d, J = 8.8 Hz, 2H), 7.02-6.96 (m, 4H), 2.04 (s, 3H), 1.83 (s,6H), 1.73 (s, 6H). LC- MS: m/z 465.2 (M − H)⁺ 378 306 XI.29

¹H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 10.19 (s, 1H), 8.06 (s, 1H),7.85 (d, J = 7.6 Hz, 1H), 7.63 (t, J = 7.2 Hz, 1H), 7.57-7.50 (m, 3H),7.21 (d, J = 8.4 Hz, 2H), 7.13-7.10 (m, 2H), 7.04 (d, J = 8.4 Hz, 2H),6.71 (d, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).LC-MS: m/z 467.3 (M + H)⁺

Experimental procedure and physiochemical characteristics of thecompound CP-453

Intermediate

The above intermediate was prepared by a procedure similar toIntermediate-XII by using Intermediate-XI.16 (0.145 g, 0.43 mmol, 1 eq.)and methyl 2-bromo-5-isobutoxybenzoate (0.125 g, 0.43 mmol, 1 eq.) toafford title product as brown solid (0.05 g, 22%). ¹H NMR (400 MHz,DMSO-d₆): δ 8.79 (s, 1H), 7.54-7.52 (m, 1H), 7.44-7.42 (m, 1H),7.28-6.98 (m, 9H), 3.85 (s, 3H), 3.80 (d, J=2.4 Hz, 2H), 3.37 (s, 3H),2.04 (s, 3H), 2.00-1.96 (m, 1H), 1.83 (s, 6H), 1.72 (s, 6H), 0.97 (d,J=6.4 Hz, 6H).

Final Compound

The above compound was prepared by a procedure similar to the onedescribed in compound-24 by using appropriate reagents in the presenceof suitable solvents at appropriate reaction conditions. Thephysiochemical characteristics of the compound also summarized.

¹H NMR (400 MHz, DMSO-d₆): δ 13.10 (s, 1H), 9.12 (s, 1H), 7.37 (d, J=2.0Hz, 1H), 7.23 (d, J=8.4 Hz, 2H), 7.10 (d, J=9.2 Hz, 2H), 7.05 (dd,J₁=2.8 Hz, J₂=9.2 Hz, 2H), 6.97 (d, J=8.8 Hz, 2H), 6.89 (d, J=8.8 Hz,2H), 3.68 (d, J=6.4 Hz, 2H), 3.21 (s, 3H), 2.04 (s, 3H), 2.01-1.98 (m,1H), 1.83 (d, J=2.6 Hz, 6H), 1.72 (s, 6H), 0.97 (d, J=6.8 Hz, 6H).LC-MS: 525.3 (M+H)⁺

Biological Assays In Vitro Palmitoylation

Recombinant GST-TEAD2 or His₆TEAD2 (500 ng) protein was pre-incubatedwith the compounds at indicated concentrations for 15 min. and thenincubated with 1 μM of alkyne palmitoyl-5 CoA (Cayman Chemical) for 30min or 50 mM MES, pH 6.4, followed by Click reaction with biotin-azideas previously described (Zheng, B. et al., J. Am. Chem. Soc., 2013, 135,7082-7085). Click reaction was performed with 100 μM biotin-azide, 1 mMtris(2-carboxyethyl) phosphine hydrochloride (TCEP), 100 μMtris[(1-benzyl-1H-1,2,3-triazol-4-yl) methyl] amine (TBTA) and 1 mMCuSO₄ for 1 h at RT.

The reactions were terminated by the addition of 12 μL of 6×SDS-sampleloading buffer (50 mM Tris-HCl, pH 6.8, 6% SDS, 48% Glycerol, 0.03%Bromophenol Blue, 30 mM EDTA, 9% MeSH). Samples were analysed bySDS-PAGE and Western blot was performed by probing with streptavidin HRPand histidine HRP antibodies independently. Bands intensity obtainedfrom streptavidin blot were quantified using BIORAD, Gel doc system andthe percentage of inhibition of Tead2 auto palmitoylation is determinedby comparing to the DMSO control treated samples.

These compounds were tested for activity in inhibiting TEAD2palmitoylation in the assay described above. The data for the compoundsis provided in below table as a percentage of inhibition of TEAD2palmitoylation by the compound at a concentration of 10 PM.

Cell Proliferation

HuH7 cells (or other cells) are cultured in DMEM supplemented with 10%FBS. The cells are seeded in 96-wells with 5000 cells/well density.After cell attached to the wells, compounds in DMSO solution were added(1% DMSO concentration) to the cells with serial dilutions for theindicated final concentration. The cells were further incubated for 3days. The cell viability is then determined using CellTiter Glo, MTT orcrystal violet staining. The inhibition curve is plotted by usingGraphPad.

qRT-PCR

YAP target gene expression was analyzed with a LightCycler 480 (Roche).Total RNA was isolated from cells using TRIzol (Life Technologies) andthen used to produce cDNA with the Transcriptor First Strand cDNASynthesis Kit (Roche). The resulting cDNA was then used in reactionswith the LightCycler 480 SYBR Green I Master mix (Roche) with probesdetecting CTGF or CYR61, and GAPDH.

CMP Assay

7-Diethylamino-3-(4′-Maleimidylphenyl)-4-Methylcoumarin (CPM), whichreacts with thiol of CoA liberated in the enzymatic reaction, and givesfluorescent signal (excitation ˜350-380, emission-460-480). The assaydetects the product (free CoA) which is produced from palmitoyl-CoA as amethod to detect the enzymatic activity. Test compounds that inhibitTEAD activity are therefore able to block the CMP fluorescent signal.

TEAD2/4 protein (10 μL of a 50 ng/μL solution) and a solution the testcompound (0.5 μL, variable concentration) were pre-incubated for 30 minat r.t. A mixture prepared from MES pH 6.4 buffer (6.5 μL of a 50 mMsolution), EDTA (1 μL of a 20 mM solution), palmitoyl-CoA (1 μL of a 20μM solution), and7-diethylamino-3-(4′-maleimidylphenyl)-4-methylcoumarin (1 μL of a 10 μMsolution) was added and the resulting mixture was mixed well using apipette. The solution was then incubated at r.t. for 30-120 min. in thedark, and fluorescence was detected at 350 nm every 30 min. until thefluorescence signal is saturated. An IC₅₀ for the ability of thecompound to inhibit fluorescence is calculated from the results.

Results of the biological assays are shown in FIGS. 3-12 and Table 1 andTable 2.

Compounds Active as TEAD Palmitoylation Inhibitors

The Example compounds were tested for activity in inhibiting TEAD2palmitoylation in the assay and CMP assay described above. The data forthe compounds provided in Table 1 as a percentage of inhibition of TEAD2palmitoylation by the compound at a concentration of 10 μM or the IC50in the CMP assay.

TABLE 1 Activity of Compounds as TEAD Palmitoylation Inhibitors % ofinhibition of TEAD2 Compound structure palmitoylation at 10 μM CMP IC₅₀(μM)

 50

1025

 70 5.09

  5

  5

 80

 20

 20

 20

  8

 80

 100

 100

TABLE 2 Activity of Compounds as TEAD2 Palmitoylation Inhibitors % ofinhibition of Cmpd. TEAD2 palmitoylation CP No Structure at 10 μM orIC₅₀ μM  51  1

 10  54  2

 0  57  3

 0  68  4

 0  70  5

 0  79  6

 0  85  7

 30 104  8

NA 201  9

 76 225  10

 0 264  11

 0 238  12

 85 347  13

 26 352  14

 0 375  15

 12 354  16

 0 381  17

 7 351  18

 35 406  19

 35  86  20

NA  87  21

NA 231  22

 74  82  23

NA  55  24

 56  52  25

 90  58  26

 90  59  27

 90  60  28

 10  61  29

 90  62  30

 91  64  31

99, 84, 82, 0.377 μM  65  32

 60  66  33

 50  67  34

 14  69  35

63, 86  71  36

100  80  37

 30  83  38

 7  88  39

 59  89  40

 43  93  41

 52  98  42

NA  99  43

NA 100  44

NA 101  45

NA 102  46

 76 103  47

 83 106  48

 87 107  49

NA 108  50

 0 113  51

 79 114  52

 79 115  53

 5 116  54

NA 117  55

NA 118  56

 0 121  57

NA 122  58

 60 124  59

 99 125  60

100 126  61

 70 127  62

 65 128  63

NA 129  64

 0 130  65

 74 131  66

 25 134  67

NO 135  68

YES 136  69

NO 138  70

NO 139  71

YES 140  72

NO 141  73

NO 142  74

 31 143  75

 63 144  76

 34 145  77

 52 146  78

NO 148  79

 45 149  80

 40 151  81

 78 156  82

 67 157  83

 65 158  84

 98 159  85

 20 160  86

 54 161  87

 4 162  88

 12 163  89

 90 168  90

98, 0.446 μM 169  91

 97 170  92

 90 172  93

 72 173  94

 91 174  95

 97 177  96

 96 178  97

 60 182 294  98

 89 183  99

 85 184 100

100, 0.207 μM 185 101

 62 186 102

 77 187 103

 53 191 104

 80 192 105

 96 194 106

 0 195 107

 14 197 108

 86 198 109

100, 0.346 μM 199 110

 85 200 111

 80 202 112

100, 0.268 μM 203 113

100 204 114

 98 205 115

 67 206 116

 91 207 117

 9 210 118

 78 211 119

100, 0.106 μM 212 120

 79 213 121

 80 214 122

 95 215 123

 88 217 124

 86 218 125

96, 0.771 μM 219 126

 86 220 127

 27 221 128

 92 226 129

 41 227 130

100 228 131

 37 233 132

100 236 133

 93 240 134

 0 241 135

100 243 136

 99 244 137

 99 245 138

 24 246 139

95, 0.312 μM 247 140

 99 248 141

 95 249 142

 65 250 143

 22 252 144

100 254 145

61, 84 255 146

 64 258 147

 70 259 148

56, 69 260 149

 40 261 150

100 263 151

101 266 152

102 267 153

100 268 154

58, 43 270 155

 99 271 156

 92 272 157

 80 273 158

100 274 159

 41 275 160

 84 276 161

17, 43 277 162

25, 88 278 163

 85 279 164

 20 282 165

 85 284 166

 98 285 167

 43 286 168

97, 0.173 μM 287 169

 42 288 170

 62 289 171

 75 290 172

100 291 173

 51 292 174

 85 293 175

 70 294 176

 89 295 177

 56 296 178

100, 0.227 μM 297 179

92, 35 298 180

 81 299 181

49, 41 300 182

 54 301 183

100, 96 302 184

 71 303 185

66, 91 304 186

 76 305 187

 57 306 188

101 307 189

 34 308 190

 85 309 191

 85 310 192

 99 311 193

 86 312 194

 20 313 195

 0 314 196

100 315 197

100 316 198

 99 317 199

 6 318 200

 32 319 201

 43 320 202

 49 321 203

 95 322 204

 99 323 205

 74 324 206

 52 325 207

 99 326 208

100 327 209

 54 328 210

100 329 211

 67 330 212

 77 331 213

 90 333 214

88, 73 334 215

 87 335 216

 89 336 217

 55 337 218

 0 338 219

 0 339 220

 10 340 221

 61 341 222

 45 342 223

100 343 224

 81 344 225

 84 345 226

 17 346 227

 58 349 228

 89 350 229

 91 353 230

 0 355 231

 0 356 232

 33 357 233

 9 358 234

 64 359 235

 84 360 236

 62 361 237

 93 362 238

100 363 239

98, 100 364 240

 62 366 241

100 367 242

35, 58 369 243

 67 370 244

 8 371 245

 87 372 246

 99 373 247

 95 376 248

 32 377 249

 1 379 250

89, 0.274 μM 380 251

 27 382 252

100, 0.053 μM 383 253

100, 0.099 μM 384 254

100, 0.297 μM 385 255

 50 386 256

 46 387 257

 55 388 258

 0 389 259

 83 392 260

 71 393 261

 98 394 262

 85 395 263

 59 396 264

 0 397 265

 78 398 266

 81 407 267

 36 408 268

 10 420 269

100  72 270

 23  94 271

NA 111 272

 77 112 273

 50 120 274

 50 123 275

 76 164 276

 52 208 277

 0 209 278

 28 605 429

 47 606 430

 63 607 431

 37 653 432

 24 109 279

NA 230 280

 0 152 281

 98 155 282

 14 153 283

89, 0.064 μM 154 284

 97 175 285

 9 540 440

 75 559 441

 79 119 286

 98  90 287

 17  96 288

NA 105 289

NA 110 290

 99 132 291

 14 133 292

 67 176 293

 86 216 294

 96 229 295

 53 237 296

 88 239 297

 69 348 298

100 378 299

 97 453

 0

TABLE 3 Activity of Compounds as TEAD2 Palmitoylation Inhibitors % ofinhibition of TEAD2 TEAD2 palmitoylation palmitoylation CP Structure at10 μM IC50 CP- 472

1 CP- 473

50 CP- 516

20 CP- 521

93 1.45 CP- 522

96 1.53 CP- 525

PPT CP- 526

23 CP- 528

76 0.38 CP- 529

29 CP- 531

20 CP- 534

31 CP- 535

54 CP- 536

84 CP- 537

73 CP- 538

85 0.68 CP- 540

75 CP- 541

80 CP- 542

49 CP- 543

98 CP- 544

98 CP- 545

6 CP- 546

97 CP- 547

18 CP- 548

86 0.45 CP- 549

85 2.4 CP- 550

96 0.79 CP- 551

91 0.002 CP- 552

74 CP- 553

100 0.59 CP- 554

96 0.01 CP- 555

100 0.01 CP- 556

61 CP- 557

34 CP- 558

66 CP- 559

79 CP- 560

90 0.011 CP- 561

90 CP- 563

80 CP- 564

89 CP- 565

100 0.51 CP- 566

99 0.38 CP- 567

6 CP- 568

46 CP- 569

59 CP- 570

73 0.65 CP- 571

94 0.36 CP- 572

72 CP- 573

74 CP- 574

91 CP- 575

47 CP- 576

42 CP- 577

79 CP- 578

31 CP- 579

61 CP- 580

58 CP- 581

40 CP- 582

0 CP- 583

96 0.23 CP- 584

85 0.21 CP- 585

86 0.32 CP- 586

40 CP- 587

36 CP- 588

36 CP- 589

97 1.57 CP- 590

96 0.22 CP- 591

88 CP- 592

40 CP- 593

78 0.03 CP- 594

46 CP- 595

51 CP- 596

48 CP- 597

63 CP- 598

74 0.05 CP- 599

57 CP- 600

37 CP- 601

46 CP- 602

5 CP- 603

83 CP- 605

47 CP- 606

63 CP- 607

37 CP- 608

43 CP- 609

54 CP- 612

86 CP- 613

83 CP- 614

83 CP- 615

82 CP- 616

73 CP- 617

76 CP- 618

31 CP- 619

96 0.75 CP- 620

0 CP- 621

47 CP- 622

94 CP- 623

73 CP- 624

15 CP- 625

87 CP- 626

87 0.382 CP- 627

51 CP- 628

40 CP- 629

24 CP- 630

39 CP- 631

81 CP- 632

73 CP- 633

25 CP- 634

32 CP- 635

27 CP- 636

68 CP- 637

5 CP- 638

67 CP- 640

20 CP- 641

69 CP- 642

55 CP- 643

89 CP- 646

39 CP- 647

87 CP- 648

89 CP- 649

99 CP- 650

93 CP- 651

85 CP- 652

37 CP- 653

24 CP- 654

36 CP- 655

97 CP- 656

90 CP- 657

18 CP- 659

46 CP- 660

66 CP- 661

77 CP- 662

88 CP- 663

45 CP- 664

50 CP- 665

96 CP- 666

79 CP- 669

75 CP- 671

97 CP- 672

55 CP- 673

15 CP- 675

83 CP- 676

97 CP- 677

96 CP- 678

59 CP- 679

81 CP- 680

52 CP- 681

8 CP- 682

51 CP- 688

17 CP- 694

79 CP- 644

Various modifications of the invention, in addition to those describedherein, will be apparent to those skilled in the art from the foregoingdescription. Such modifications are also intended to fall within thescope of the appended claims. Each reference, including withoutlimitation all patent, patent applications, and publications, cited inthe present application is incorporated herein by reference in itsentirety.

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein: L¹ is absent, ora group of formula N(R^(N)) or C(O); D is a group of formula (D1), (D2),(D3), (D4), (D5), (D6) or (D7):

m is 1, 2 or 3; A¹ is C(O)R¹, S(O)₂R¹, NHC(O)R¹, (C₁₋₃ alkylene)-C(O)R¹,NH(C₁₋₃ alkylene)-C(O)R¹, CN, NO₂, 5-10 membered heteroaryl, 4-10membered heterocycloalkyl, (C₁₋₃ alkylene)-5-10 membered heteroaryl, or(C₁₋₃ alkylene)-4-10 membered heterocycloalkyl, wherein the (C₁₋₃alkylene) group of the (C₁₋₃ alkylene)-C(O)R¹ group forming A¹ isunsubstituted or substituted by 1, 2, 3, 4 or 5 substituents eachindependently selected from halogen, OR^(a1), NR^(c1)R^(d1),NR^(a1)(CO)(C₁₋₆ alkyl), and NR^(a1)(CO)O(C₁₋₆ alkyl); and wherein the5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C₁₋₃alkylene)-5-10 membered heteroaryl, or (C₁₋₃ alkylene)-4-10 memberedheterocycloalkyl forming A¹ is unsubstituted or substituted by 1, 2, 3,4 or 5 substituents each independently selected from halogen, OR^(a1),SR^(a1), C(O)OR^(a1), NR^(c1)R^(d1), and C(O)NR^(c1)R^(d1); L² isabsent, or a group of formula N(R^(N)), O, or C(O); L³ is absent or agroup of formula CH₂, C≡C, N(R^(N)) or C(O); each R^(N) is independentlyH, C₁₋₆ alkyl, C(O)C₁₋₆ alkyl, or C(O)OC₁₋₆ alkyl; R¹ is H, C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, Cy^(1A), OH, OC₁₋₆ alkyl, OCy^(1A)O(C₁₋₃alkylenyl)Cy^(1A), NH₂, NHC₁₋₆ alkyl, N(C₁₋₆ alkyl)₂, NHCy^(1A), NH(C₁₋₃alkylenyl)Cy^(1A), N(C₁₋₆ alkyl)Cy^(1A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1A), wherein each of the C₁₋₆ alkyl forming R¹ isunsubstituted or substituted by 1, 2, 3, 4 or 5 substituents eachindependently selected from halogen, OR^(a1), SR^(a1), andNR^(c1)R^(d1); Cy^(1A) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 memberedheteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C₆₋₁₀aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or 4-10 memberedheterocycloalkyl forming Cy^(1A) is unsubstituted or substituted by 0, 1or 2 Cy^(1B) and 0, 1, 2, 3, 4 or 5 substituents each independentlyselected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1) and C₁₋₆alkyl that is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); each Cy^(1B) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each ofthe C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or 4-10membered heterocycloalkyl forming Cy^(1B) is unsubstituted orsubstituted by 1, 2, 3, 4 or 5 substituents each independently selectedfrom unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and C₁₋₆ alkyl thatis substituted by 1, 2, or 3 substituents each independently selectedfrom halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1);A² is CR² or N; A³ is CR³ or N; A⁴ is CR⁴ or N; A⁵ is CR⁵ or N; A⁶ isCR⁶ or N; A⁷ is CR⁷ or N; A⁸ is CR⁸ or N; A⁹ is CR⁹ or N; A¹⁰ is CR¹⁰ orN; A^(D41) is CH, C(C₁₋₆ alkyl) or N; A^(D42) is CH₂, NH or NC₁₋₆ alkyl;R² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen,C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R³ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1) or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),C(O)OR^(a1), C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁵ is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1) or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁶ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), S(O)₂R^(b1), S(O)₂NR^(c1)R^(d1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1), Cy^(7A), OCy^(7A), O(C₁₋₃ alkylenyl)Cy^(7A),C(O)OCy^(7A), C(O)O(C₁₋₃ alkylenyl)Cy^(7A), NHCy^(7A), NH(C₁₋₃alkylenyl)Cy^(7A), N(C₁₋₆ alkyl)Cy^(7A), N(C(O)C₁₋₆ alkyl)Cy^(7A),N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7A), C(O)NHCy^(7A), C(O)NH(C₁₋₃alkylenyl)Cy^(7A), C(O)N(C₁₋₆ alkyl)Cy^(7A), C(O)N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7A), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁷ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), S(O)₂NR^(c1)R^(d1),C(O)NR^(c1)R^(d1), Cy^(7A), OCy^(7A), O(C₁₋₃ alkylenyl)Cy^(7A),C(O)OCy^(7A), C(O)O(C₁₋₃ alkylenyl)Cy^(7A), NHCy^(7A), NH(C₁₋₃alkylenyl)Cy^(7A), N(C₁₋₆ alkyl)Cy^(7A), N(C(O)C₁₋₆ alkyl)Cy^(7A),N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7A), C(O)NHCy^(7A), C(O)NH(C₁₋₃alkylenyl)Cy^(7A), C(O)N(C₁₋₆ alkyl)Cy^(7A), C(O)N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7A) or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1) and NR^(c1)R^(d1); Cy^(7A) is C₆₋₁₀ aryl, C₃₋₁₅cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl,wherein each of the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 memberedheteroaryl, or 4-10 membered heterocycloalkyl forming Cy^(7A) isunsubstituted or substituted by 0, 1 or 2 substituents selected fromCy^(7B), OCy^(7B), NHCy^(7B), and C(O)NHCy^(7B), and 0, 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); each Cy^(7B) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each ofthe C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or 4-10membered heterocycloalkyl forming Cy^(7B) is unsubstituted orsubstituted by 1, 2, 3, 4 or 5 substituents each independently selectedfrom unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1), and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), NR^(c1)R^(d1); R⁸ is H, unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),S(O)₂NR^(c1)R^(d1), SR^(a1), NR^(c1)R^(d1), , NR^(c1)S(O)₂R^(b1),C(O)OR^(a1), C(O)NR^(c1)R^(d1), Cy^(8A), OH, OCy^(8A), O(C₁₋₃alkylenyl)Cy^(8A), C(O)OCy^(8A), C(O)O(C₁₋₃ alkylenyl)Cy^(8A),NHCy^(8A), N(Cy^(8A))₂, NH(C₁₋₃ alkylenyl)Cy^(8A), N(C₁₋₆ alkyl)Cy^(8A),N(C(O)C₁₋₆ alkyl)Cy^(8A), SO₂NHCy^(8A), N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8A), C(O)NHCy^(8A), C₁₋₃ alkylene-C(O)NHCy^(8A),C(O)NH(C₁₋₃ alkylenyl)Cy^(8A), C(O)N(C₁₋₆ alkyl)Cy^(8A), C(O)N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(8A), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1) and NR^(c1)R^(d1); Cy^(8A) is C₆₋₁₀aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or 4-10 memberedheterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy^(8A)is unsubstituted or substituted by 0, 1 or 2 substituents selected fromCy^(8B), OCy^(8B), NHCy^(8B), and C(O)NHCy^(8B), and 0, 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); each Cy^(8B) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each ofthe C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or 4-10membered heterocycloalkyl forming Cy^(8B) is unsubstituted orsubstituted by 1, 2, 3, 4 or 5 substituents each independently selectedfrom unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1), and C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁹ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), NR^(c1)C(O)R^(b1), C(O)OR^(a1),C(O)NR^(c1)R^(d1), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R¹⁰ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); Cy^(D71) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-14 memberedheteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C₆₋₁₀aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or 4-10 memberedheterocycloalkyl forming Cy^(D71) is unsubstituted or substituted by 0,1 or 2 substituents selected from Cy^(D72), CH₂Cy^(D72), OCy^(D72),NHCy^(D72), O—C₁₋₆ alkylene-Cy^(D72), N(C₁₋₆ alkyl)Cy^(D72), N(C(O)C₁₋₆alkyl)Cy^(D72), and C(O)NHCy^(D72), and 0, 1, 2, 3, 4 or 5 substituentseach independently selected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), S(hal)₅, SR^(a1),NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆ alkyl or C₂₋₆alkenyl that is substituted by 1, 2, or 3 substituents eachindependently selected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), C(O)OR^(a1), and NR^(c1)R^(d1); each Cy^(D72) is C₆₋₁₀ aryl,C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or 4-10 memberedheterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy^(D72)is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents eachindependently selected from unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 4-10 membered heterocycloalkyl,halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),C(O)OR^(a1), C(O)NR^(c1)R^(d1), and C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from C₆₋₁₀ aryl, C₃₋₁₅cycloalkyl, 4-10 membered heterocycloalkyl, halogen, C₁₋₆ haloalkyl, CN,OR^(a1), SR^(a1), C(O)OR^(a1), and NR^(c1)R^(d1) wherein said C₆₋₁₀aryl, C₃₋₁₅ cycloalkyl, and 4-10 membered heterocycloalkyl are eachoptionally substituted with 1, 2, or 3 substituents independentlyselected from C₁₋₆ alkyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1),NR^(c1)R^(d1), C(O)OR^(a1), and C(O)NR^(c1)R^(d1); and R^(a1), R^(b1),R^(c1) and R^(d1) are each independently selected from H, C₁₋₆ alkyl,C₁₋₆ haloalkyl, HO—C₁₋₆ alkylene, amino-C₁₋₆ alkylene, C₁₋₆alkylamino-C₁₋₆ alkylene, di(C₁₋₆ alkyl)amino-C₁₋₆ alkylene, C₁₋₆alkoxy-C₁₋₆ alkylene, C₆₋₁₀ aryl, C₂₋₆ alkenyl and C₂₋₆ alkynyl; orR^(c1) and R^(d1) together with the nitrogen atom to which they are bothattached together form a 4-10 membered unsubstituted heterocycloalkylring or a heterocyclic ring that is substituted with 1, 2, or 3substituents independently selected from C₁₋₆ alkyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), andC(O)NR^(c1)R^(d1); provided: L¹ is a group of formula N(R^(N)) when L²is C(O); L¹ is a group of formula C(O) when L² is N(R^(N)); L² isabsent, or a group of formula N(R^(N)) when L¹ is C(O); L² is absent, ora group of formula C(O) when L¹ is N(R^(N)); A^(D41) is CH, C(C₁₋₆alkyl) when A^(D42) is NH or NC₁₋₆ alkyl; A^(D42) is CH₂ when A^(D41) isNH or NC₁₋₆ alkyl; no more than two of A², A³, A⁴ and A⁵ is N; no morethan two of A⁶, A⁷, A⁸, A⁹ and A¹⁰ is N; and either R¹ is present and isCy^(1A), OCy^(1A), O(C₁₋₃ alkylenyl)Cy^(1A), NHCy^(1A), NH(C₁₋₃alkylenyl)Cy^(1A), N(C₁₋₆ alkyl)Cy^(1A), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1A); or R⁷ is Cy^(7A), OCy^(7A), O(C₁₋₃ alkylenyl)Cy^(7A),C(O)OCy^(7A), C(O)O(C₁₋₃ alkylenyl)Cy^(7A), NHCy^(7A), NH(C₁₋₃alkylenyl)Cy^(7A), N(C₁₋₆ alkyl)Cy^(7A), N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7A); C(O)NHCy^(7A), C(O)NH(C₁₋₃ alkylenyl)Cy^(7A),C(O)N(C₁₋₆ alkyl)Cy^(7A), or C(O)N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7A),or R⁸ is Cy^(8A), OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), C(O)OCy^(8A),C(O)O(C₁₋₃ alkylenyl)Cy^(8A), NHCy^(8A), NH(C₁₋₃ alkylenyl)Cy^(8A),N(C₁₋₆ alkyl)Cy^(8A), N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(8A),C(O)NHCy^(8A), C(O)NH(C₁₋₃ alkylenyl)Cy^(8A), C(O)N(C₁₋₆ alkyl)Cy^(8A),or C(O)N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(8A).
 2. The compound of claim 1,wherein: R⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),C(O)OR^(a1), C(O)NR^(c1)R^(d1), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁷ is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1), Cy^(7A), OCy^(7A), O(C₁₋₃ alkylenyl)Cy^(7A),C(O)OCy^(7A), C(O)O(C₁₋₃ alkylenyl)Cy^(7A), NHCy^(7A), NH(C₁₋₃alkylenyl)Cy^(7A), N(C₁₋₆ alkyl)Cy^(7A), N(C(O)C₁₋₆ alkyl)Cy^(7A),N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7A), C(O)NHCy^(7A), C(O)NH(C₁₋₃alkylenyl)Cy^(7A), C(O)N(C₁₋₆ alkyl)Cy^(7A), C(O)N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7A) or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁸ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), Cy^(8A), OH,OCy^(8A), O(C₁₋₃ alkylenyl)Cy^(8A), C(O)OCy^(8A), C(O)O(C₁₋₃alkylenyl)Cy^(8A), NHCy^(8A), N(Cy^(8A))₂, NH(C₁₋₃ alkylenyl)Cy^(8A),N(C₁₋₆ alkyl)Cy^(8A), N(C(O)C₁₋₆ alkyl)Cy^(8A), SO₂NHCy^(8A), N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(8A), C(O)NHCy^(8A), C₁₋₃alkylene-C(O)NHCy^(8A), C(O)NH(C₁₋₃ alkylenyl)Cy^(8A), C(O)N(C₁₋₆alkyl)Cy^(8A), C(O)N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(8A), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R⁹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),C(O)OR^(a1), C(O)NR^(c1)R^(d1), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); Cy^(D7)1 is C₆₋₁₀aryl, C₃₋₁₅ cycloalkyl, 5-14 membered heteroaryl, or 4-10 memberedheterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy^(D71)is unsubstituted or substituted by 0, 1 or 2 substituents selected fromCy^(D72), CH₂Cy^(D72), OCy^(D72), NHCy^(D72), O—C₁₋₆ alkylene-Cy^(D72),N(C₁₋₆ alkyl)Cy^(D72), N(C(O)C₁₋₆ alkyl)Cy^(D72), and C(O)NHCy^(D72),and 0, 1, 2, 3, 4 or 5 substituents each independently selected fromunsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1),C(O)NR^(c1)R^(d1), and C₁₋₆ alkyl or C₂₋₆ alkenyl that is substituted by1, 2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), C(O)OR^(a1), and NR^(c1)R^(d1); eachCy^(D72) is C₆₋₁₀ aryl, C₃₋₁₅ cycloalkyl, 5-10 membered heteroaryl, or4-10 membered heterocycloalkyl, wherein each of the C₆₋₁₀ aryl, C₃₋₁₅cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkylforming Cy^(D72) is unsubstituted or substituted by 1, 2, 3, 4 or 5substituents each independently selected from unsubstituted C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₁₅ cycloalkyl, halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), C(O)OR^(a1), C(O)NR^(c1)R^(d1), andC₁₋₆ alkyl that is substituted by 1, 2, or 3 substituents eachindependently selected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), C(O)OR^(a1), and NR^(c1)R^(d1); and R^(a1), R^(b1), R^(c1) andR^(d1) are each independently selected from H, C₁₋₆ alkyl, HO—C₁₋₆alkylene, C₁₋₆ alkoxy-C₁₋₆ alkylene, C₆₋₁₀ aryl, C₂₋₆ alkenyl and C₂₋₆alkynyl; or R^(c1) and R^(d1) together with the nitrogen atom to whichthey are both attached together form a 4-10 membered unsubstitutedheterocycloalkyl ring. 3-4. (canceled)
 5. The compound orpharmaceutically acceptable salt thereof of claim 1, wherein D is agroup of formula (D1).
 6. The compound or pharmaceutically acceptablesalt thereof of claim 1, wherein D is a group of formula (D2).
 7. Thecompound or pharmaceutically acceptable salt thereof of claim 1, whereinD is a group of formula (D3). 8-30. (canceled)
 31. The compound orpharmaceutically acceptable salt thereof of claim 1, wherein D is agroup of formula (D4). 32-40. (canceled)
 41. The compound orpharmaceutically acceptable salt thereof of claim 1, wherein D is agroup of formula (D5). 42-44. (canceled)
 45. The compound orpharmaceutically acceptable salt thereof of claim 1, wherein D is agroup of formula (D6).
 46. (canceled)
 47. The compound orpharmaceutically acceptable salt thereof of claim 45, wherein m is 2.48-50. (canceled)
 51. The compound or pharmaceutically acceptable saltthereof of claim 47, wherein R¹ is NHCy^(1A). 52-53. (canceled)
 54. Thecompound or pharmaceutically acceptable salt thereof of claim 51,wherein R¹ is a group of one of the following formulae:

wherein: R¹¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B),OH, OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R¹² is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH, OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B),NHCy^(1B), NH(C₁₋₃ alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R¹³ is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH, OCy^(1B),O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃ alkylenyl)Cy^(1B), N(C₁₋₆alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(1B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R¹⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),Cy^(1B), OH, OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R¹⁵ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH, OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B),NHCy^(1B), NH(C₁₋₃ alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R¹⁶ is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH, OCy^(1B),O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃ alkylenyl)Cy^(1B), N(C₁₋₆alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(1B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R¹⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),Cy^(1B), OH, OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and R¹⁸ is H, unsubstitutedC₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN,OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH, OCy^(1B), O(C₁₋₃alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃ alkylenyl)Cy^(1B), N(C₁₋₆alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(1B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1).
 55. The compound or pharmaceutically acceptable saltthereof of claim 54, wherein R¹ is a group of one of the followingformulae:

56-118. (canceled)
 119. The compound or pharmaceutically acceptable saltthereof of claim 1, wherein the compound is a compound of one of thefollowing formulae (I-1) to (I-60):

wherein: R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R^(N), A¹, A², A³, A⁴,A⁵, A⁶, A⁷, A⁸, A⁹, A¹⁰, Cy^(1A), Cy^(1B), Cy^(7A), Cy^(7B), Cy^(8A),Cy^(8B), L¹ and L², are as defined in claim 1; L⁷ is absent, O, NH orN(C₁₋₆ alkyl); L⁸ is absent, O, NH or N(C₁₋₆ alkyl); R¹¹ is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH, OCy^(1B),O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃ alkylenyl)Cy^(1B), N(C₁₋₆alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(1B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R¹² is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),Cy^(1B), OH, OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R¹³ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH, OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B),NHCy^(1B), NH(C₁₋₃ alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R¹⁴ is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH, OCy^(1B),O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃ alkylenyl)Cy^(1B), N(C₁₋₆alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(1B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R¹⁵ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),Cy^(1B), OH, OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R¹⁶ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH, OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B),NHCy^(1B), NH(C₁₋₃ alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R¹⁷ is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(1B), OH, OCy^(1B),O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃ alkylenyl)Cy^(1B), N(C₁₋₆alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(1B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R¹⁸ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),Cy^(1B), OH, OCy^(1B), O(C₁₋₃ alkylenyl)Cy^(1B), NHCy^(1B), NH(C₁₋₃alkylenyl)Cy^(1B), N(C₁₋₆ alkyl)Cy^(1B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(1B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁷¹ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH, OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B),NHCy^(7B), NH(C₁₋₃ alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁷² is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH, OCy^(7B),O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃ alkylenyl)Cy^(7B), N(C₁₋₆alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R⁷³ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),Cy^(7B), OH, OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁷⁴ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH, OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B),NHCy^(7B), NH(C₁₋₃ alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁷⁵ is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH, OCy^(7B),O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃ alkylenyl)Cy^(7B), N(C₁₋₆alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R⁷⁶ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),Cy^(7B), OH, OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁷⁷ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH, OCy^(7B), O(C₁₋₃ alkylenyl)Cy^(7B),NHCy^(7B), NH(C₁₋₃ alkylenyl)Cy^(7B), N(C₁₋₆ alkyl)Cy^(7B), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(7B), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and R⁷⁸ is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(7B), OH, OCy^(7B),O(C₁₋₃ alkylenyl)Cy^(7B), NHCy^(7B), NH(C₁₋₃ alkylenyl)Cy^(7B), N(C₁₋₆alkyl)Cy^(7B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(7B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R⁸¹ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),Cy^(8B), OH, OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁸² is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH, OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B),NHCy^(8B), NH(C₁₋₃ alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁸³ is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH, OCy^(8B),O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃ alkylenyl)Cy^(8B), N(C₁₋₆alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(8B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R⁸⁴ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),Cy^(8B), OH, OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁸⁵ is H, unsubstituted C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1),SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH, OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B),NHCy^(8B), NH(C₁₋₃ alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆alkyl)(C₁₋₃ alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1,2, or 3 substituents each independently selected from halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); R⁸⁶ is H,unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH, OCy^(8B),O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃ alkylenyl)Cy^(8B), N(C₁₋₆alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(8B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1); R⁸⁷ is H, unsubstituted C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), NR^(c1)R^(d1),Cy^(8B), OH, OCy^(8B), O(C₁₋₃ alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃alkylenyl)Cy^(8B), N(C₁₋₆ alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃alkylenyl)Cy^(8B), or C₁₋₆ alkyl that is substituted by 1, 2, or 3substituents each independently selected from halogen, C₁₋₆ haloalkyl,CN, OR^(a1), SR^(a1), and NR^(c1)R^(d1); and R⁸⁸ is H, unsubstitutedC₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, C₁₋₆ haloalkyl, CN,OR^(a1), SR^(a1), NR^(c1)R^(d1), Cy^(8B), OH, OCy^(8B), O(C₁₋₃alkylenyl)Cy^(8B), NHCy^(8B), NH(C₁₋₃ alkylenyl)Cy^(8B), N(C₁₋₆alkyl)Cy^(8B), or N(C₁₋₆ alkyl)(C₁₋₃ alkylenyl)Cy^(8B), or C₁₋₆ alkylthat is substituted by 1, 2, or 3 substituents each independentlyselected from halogen, C₁₋₆ haloalkyl, CN, OR^(a1), SR^(a1), andNR^(c1)R^(d1). 120-124. (canceled)
 125. The compound or pharmaceuticallyacceptable salt thereof of claim 1, wherein the compound is a compoundof one of the following formulae:


126. A compound or claim 1, or a pharmaceutically acceptable saltthereof, wherein the compound of formula (I) is selected from any one ofthe following compounds:


127. A pharmaceutical composition comprising a compound of claim 1, or apharmaceutically acceptable salt thereof, and at least onepharmaceutically acceptable carrier. 128-129. (canceled)
 130. A methodof treating cancer comprising administering to a patient in need of suchtreatment a therapeutically effective amount of a compound of claim 1,or a pharmaceutically acceptable salt thereof.
 131. The method of claim130, wherein the cancer is a solid tumor or a hematological cancer. 132.The method of claim 130, wherein the cancer is prostate cancer, coloncancer, esophageal cancer, endometrial cancer, ovarian cancer, uterinecancer, renal cancer, hepatic cancer, pancreatic cancer, gastric cancer,breast cancer, lung cancer, cancer of the head or neck, thyroid cancer,glioblastoma, sarcoma, bladder cancer, lymphoma, leukemia, acutelymphoblastic leukemia, acute myelogenous leukemia, chronic lymphocyticleukemia, chronic myelogenous leukemia, diffuse large-B cell lymphoma,mantle cell lymphoma, non-Hodgkin lymphoma, Hodgkin lymphoma or multiplemyeloma.
 133. The method of claim 130, wherein the cancer ishepatocellular carcinoma, medulloblastoma, cutaneous squamous cellcarcinoma, lung cancer, pancreatic cancer, esophagus cancer, livercancer, colon cancer, melanoma, or uveal melanoma.